Advertisement

Seminars in Immunopathology

, Volume 40, Issue 3, pp 249–259 | Cite as

Skin neurogenic inflammation

  • Jae Eun Choi
  • Anna Di Nardo
Review

Abstract

The epidermis closely interacts with nerve endings, and both epidermis and nerves produce substances for mutual sustenance. Neuropeptides, like substance P (SP) and calcitonin gene-related protein (CGRP), are produced by sensory nerves in the dermis; they induce mast cells to release vasoactive amines that facilitate infiltration of neutrophils and T cells. Some receptors are more important than others in the generation of itch. The Mas-related G protein-coupled receptors (Mrgpr) family as well as transient receptor potential ankyrin 1 (TRPA1) and protease activated receptor 2(Par2) have important roles in itch and inflammation. The activation of MrgprX1 degranulates mast cells to communicate with sensory nerve and cutaneous cells for developing neurogenic inflammation. Mrgprs and transient receptor potential vanilloid 4 (TRPV4) are crucial for the generation of skin diseases like rosacea, while SP, CGRP, somatostatin, β-endorphin, vasoactive intestinal peptide (VIP), and pituitary adenylate cyclase-activating polypeptide (PACAP) can modulate the immune system during psoriasis development. The increased level of SP, in atopic dermatitis, induces the release of interferon (IFN)-γ, interleukin (IL)-4, tumor necrosis factor (TNF)-α, and IL-10 from the peripheral blood mononuclear leukocytes. We are finally starting to understand the intricate connections between the skin neurons and resident skin cells and how their interaction can be key to controlling inflammation and from there the pathogenesis of diseases like atopic dermatitis, psoriasis, and rosacea.

References

  1. 1.
    Huynh M, Gupta R, Koo JY (2013) Emotional stress as a trigger for inflammatory skin disorders. Semin Cutan Med Surg 32(2):68–72PubMedCrossRefGoogle Scholar
  2. 2.
    Chen Y, Lyga J (2014) Brain-skin connection: stress, inflammation and skin aging. Inflamm Allergy Drug Targets 13(3):177–190PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Stricker (1876) Mikroskopische Studien iiber Wachstum und Wechsel der Haai'e,. In: Ebner V (ed) manual of human embriology, vol xxiv. Sitz. Her. d. K. Akad. d. Wiss., Wien,Google Scholar
  4. 4.
    Bayliss WM, Starling EH (1901) The movements and innervation of the small intestine. J Physiol 26(3–4):125–138.  https://doi.org/10.1113/jphysiol.1901.sp000827 PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Peters EM (2012) The neuroendocrine-immune connection regulates chronic inflammatory disease in allergy. Chem Immunol Allergy 98:240–252.  https://doi.org/10.1159/000336527 PubMedCrossRefGoogle Scholar
  6. 6.
    Chiu IM, von Hehn CA, Woolf CJ (2012) Neurogenic inflammation and the peripheral nervous system in host defense and immunopathology. Nat Neurosci 15(8):1063–1067.  https://doi.org/10.1038/nn.3144 PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Szolcsanyi J (1996) Capsaicin-sensitive sensory nerve terminals with local and systemic efferent functions: facts and scopes of an unorthodox neuroregulatory mechanism. Prog Brain Res 113:343–359PubMedCrossRefGoogle Scholar
  8. 8.
    Liezmann C, Klapp B, Peters EM (2011) Stress, atopy and allergy: a re-evaluation from a psychoneuroimmunologic persepective. Derm Endocrinol 3(1):37–40.  https://doi.org/10.4161/derm.3.1.14618 CrossRefGoogle Scholar
  9. 9.
    Peters EM, Ericson ME, Hosoi J, Seiffert K, Hordinsky MK, Ansel JC, Paus R, Scholzen TE (2006) Neuropeptide control mechanisms in cutaneous biology: physiological and clinical significance. J Investig Dermatol 126(9):1937–1947.  https://doi.org/10.1038/sj.jid.5700429 PubMedCrossRefGoogle Scholar
  10. 10.
    Botchkarev VA, Yaar M, Peters EM, Raychaudhuri SP, Botchkareva NV, Marconi A, Raychaudhuri SK, Paus R, Pincelli C (2006) Neurotrophins in skin biology and pathology. J Investig Dermatol 126(8):1719–1727.  https://doi.org/10.1038/sj.jid.5700270 PubMedCrossRefGoogle Scholar
  11. 11.
    Roosterman D, Goerge T, Schneider SW, Bunnett NW, Steinhoff M (2006) Neuronal control of skin function: the skin as a neuroimmunoendocrine organ. Physiol Rev 86(4):1309–1379.  https://doi.org/10.1152/physrev.00026.2005 PubMedCrossRefGoogle Scholar
  12. 12.
    Cevikbas F, Steinhoff A, Homey B, Steinhoff M (2007) Neuroimmune interactions in allergic skin diseases. Curr Opin Allergy Clin Immunol 7(5):365–373.  https://doi.org/10.1097/ACI.0b013e3282a644d2 PubMedCrossRefGoogle Scholar
  13. 13.
    Park YM, Kim CW The effects of substance P and vasoactive intestinal peptide on interleukin-6 synthesis in cultured human keratinocytes. J Dermatol Sci 22(1):17–23.  https://doi.org/10.1016/S0923-1811(99)00038-9
  14. 14.
    Song IS, Bunnett NW, Olerud JE, Harten B, Steinhoff M, Brown JR, Sung KJ, Armstrong CA, Ansel JC (2000) Substance P induction of murine keratinocyte PAM 212 interleukin 1 production is mediated by the neurokinin 2 receptor (NK-2R). Exp Dermatol 9(1):42–52PubMedCrossRefGoogle Scholar
  15. 15.
    Burbach GJ, Kim KH, Zivony AS, Kim A, Aranda J, Wright S, Naik SM, Caughman SW, Ansel JC, Armstrong CA The neurosensory tachykinins substance P and neurokinin A directly induce keratinocyte nerve growth factor. J Investig Dermatol 117(5):1075–1082.  https://doi.org/10.1046/j.0022-202x.2001.01498.x
  16. 16.
    Dallos A, Kiss M, Polyánka H, Dobozy A, Kemény L, Husz S Effects of the neuropeptides substance P, calcitonin gene-related peptide, vasoactive intestinal polypeptide and galanin on the production of nerve growth factor and inflammatory cytokines in cultured human keratinocytes. Neuropeptides 40(4):251–263.  https://doi.org/10.1016/j.npep.2006.06.002
  17. 17.
    Nakano Y (2004) Stress-induced modulation of skin immune function: two types of antigen-presenting cells in the epidermis are differentially regulated by chronic stress. Br J Dermatol 151(1):50–64.  https://doi.org/10.1111/j.1365-2133.2004.05980.x PubMedCrossRefGoogle Scholar
  18. 18.
    Beresford L, Orange O, Bell EB, Miyan JA (2004) Nerve fibres are required to evoke a contact sensitivity response in mice. Immunology 111(1):118–125PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Joachim RA, Handjiski B, Blois SM, Hagen E, Paus R, Arck PC Stress-induced neurogenic inflammation in murine skin skews dendritic cells towards maturation and migration. Am J Pathol 173(5):1379–1388.  https://doi.org/10.2353/ajpath.2008.080105
  20. 20.
    Rosa AC, Fantozzi R (2013) The role of histamine in neurogenic inflammation. Br J Pharmacol 170(1):38–45.  https://doi.org/10.1111/bph.12266 PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Liu JY, Hu JH, Zhu QG, Li FQ, Sun HJ (2006) Substance P receptor expression in human skin keratinocytes and fibroblasts. Br J Dermatol 155(4):657–662.  https://doi.org/10.1111/j.1365-2133.2006.07408.x PubMedCrossRefGoogle Scholar
  22. 22.
    Bae SJ, Matsunaga Y, Takenaka M, Tanaka Y, Hamazaki Y, Shimizu K, Katayama I (2002) Substance P induced preprotachykinin-a mRNA, neutral endopeptidase mRNA and substance P in cultured normal fibroblasts. Int Arch Allergy Immunol 127(4):316–321 57749PubMedCrossRefGoogle Scholar
  23. 23.
    Brain SD, Williams TJ (1989) Interactions between the tachykinins and calcitonin gene-related peptide lead to the modulation of oedema formation and blood flow in rat skin. Br J Pharmacol 97(1):77–82PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Saria A (1984) Substance P in sensory nerve fibres contributes to the development of oedema in the rat hind paw after thermal injury. Br J Pharmacol 82(1):217–222PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Lindsey KQ, Caughman SW, Olerud JE, Bunnett NW, Armstrong CA, Ansel JC (2000) Neural regulation of endothelial cell-mediated inflammation. J Investig Dermatol Symp Proc 5(1):74–78.  https://doi.org/10.1046/j.1087-0024.2000.00013.x PubMedCrossRefGoogle Scholar
  26. 26.
    Castellani ML, Galzio RJ, Felaco P, Tripodi D, Toniato E, De Lutiis MA, Conti F, Fulcheri M, Conti C, Theoharides TC, Caraffa A, Antinolfi P, Felaco M, Tete S, Pandolfi F, Shaik-Dasthagirisaheb YB (2010) VEGF, substance P and stress, new aspects: a revisited study. J Biol Regul Homeost Agents 24(3):229–237PubMedGoogle Scholar
  27. 27.
    Kohara H, Tajima S, Yamamoto M, Tabata Y (2010) Angiogenesis induced by controlled release of neuropeptide substance P. Biomaterials 31(33):8617–8625.  https://doi.org/10.1016/j.biomaterials.2010.07.079 PubMedCrossRefGoogle Scholar
  28. 28.
    Mishima T, Ito Y, Hosono K, Tamura Y, Uchida Y, Hirata M, Suzsuki T, Amano H, Kato S, Kurihara Y, Kurihara H, Hayashi I, Watanabe M, Majima M (2011) Calcitonin gene-related peptide facilitates revascularization during hindlimb ischemia in mice. Am J Phys Heart Circ Phys 300(2):H431–H439.  https://doi.org/10.1152/ajpheart.00466.2010 CrossRefGoogle Scholar
  29. 29.
    Zhou Z, Hu CP, Wang CJ, Li TT, Peng J, Li YJ (2010) Calcitonin gene-related peptide inhibits angiotensin II-induced endothelial progenitor cells senescence through up-regulation of klotho expression. Atherosclerosis 213(1):92–101.  https://doi.org/10.1016/j.atherosclerosis.2010.08.050 PubMedCrossRefGoogle Scholar
  30. 30.
    Ding W, Stohl LL, Wagner JA, Granstein RD (2008) Calcitonin gene-related peptide biases Langerhans cells toward Th2-type immunity. J Immunol (Baltimore, Md : 1950) 181(9):6020–6026CrossRefGoogle Scholar
  31. 31.
    McLatchie LM, Fraser NJ, Main MJ, Wise A, Brown J, Thompson N, Solari R, Lee MG, Foord SM (1998) RAMPs regulate the transport and ligand specificity of the calcitonin-receptor-like receptor. Nature 393(6683):333–339.  https://doi.org/10.1038/30666 PubMedCrossRefGoogle Scholar
  32. 32.
    Garret C, Carruette A, Fardin V, Moussaoui S, Peyronel JF, Blanchard JC, Laduron PM (1991) Pharmacological properties of a potent and selective nonpeptide substance P antagonist. Proc Natl Acad Sci U S A 88(22):10208–10212PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Stander S, Siepmann D, Herrgott I, Sunderkotter C, Luger TA (2010) Targeting the neurokinin receptor 1 with aprepitant: a novel antipruritic strategy. PLoS One 5(6):e10968.  https://doi.org/10.1371/journal.pone.0010968 PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Wrobel Goldberg S, Silberstein SD (2015) Targeting CGRP: a new era for migraine treatment. CNS drugs 29(6):443–452.  https://doi.org/10.1007/s40263-015-0253-z PubMedCrossRefGoogle Scholar
  35. 35.
    Ding W, Manni M, Stohl LL, Zhou XK, Wagner JA, Granstein RD (2012) Pituitary adenylate cyclase-activating peptide and vasoactive intestinal polypeptide bias Langerhans cell Ag presentation toward Th17 cells. Eur J Immunol 42(4):901–911.  https://doi.org/10.1002/eji.201141958 PubMedCrossRefGoogle Scholar
  36. 36.
    Jans R, Sartor M, Jadot M, Poumay Y (2004) Calcium entry into keratinocytes induces exocytosis of lysosomes. Arch Dermatol Res 296(1):30–41.  https://doi.org/10.1007/s00403-004-0469-0 PubMedCrossRefGoogle Scholar
  37. 37.
    Zhao P, Metcalf M, Bunnett NW (2014) Biased signaling of protease-activated receptors. Front Endocrinol 5:67.  https://doi.org/10.3389/fendo.2014.00067 CrossRefGoogle Scholar
  38. 38.
    Chen Y, Yang C, Wang ZJ (2011) Proteinase-activated receptor 2 sensitizes transient receptor potential vanilloid 1, transient receptor potential vanilloid 4, and transient receptor potential ankyrin 1 in paclitaxel-induced neuropathic pain. Neuroscience 193:440–451.  https://doi.org/10.1016/j.neuroscience.2011.06.085 PubMedCrossRefGoogle Scholar
  39. 39.
    Steinhoff M, Neisius U, Ikoma A, Fartasch M, Heyer G, Skov PS, Luger TA, Schmelz M (2003) Proteinase-activated receptor-2 mediates itch: a novel pathway for pruritus in human skin. J Neurosci Off J Soc Neurosci 23(15):6176–6180CrossRefGoogle Scholar
  40. 40.
    Fu Q, Cheng J, Gao Y, Zhang Y, Chen X, Xie J (2015) Protease-activated receptor 4: a critical participator in inflammatory response. Inflammation 38(2):886–895.  https://doi.org/10.1007/s10753-014-9999-6 PubMedCrossRefGoogle Scholar
  41. 41.
    Cocks TM, Moffatt JD (2000) Protease-activated receptors: sentries for inflammation? Trends Pharmacol Sci 21(3):103–108PubMedCrossRefGoogle Scholar
  42. 42.
    Gouin O, Lebonvallet N, L'Herondelle K, Le Gall-Ianotto C, Buhe V, Plee-Gautier E, Carre JL, Lefeuvre L, Misery L (2015) Self-maintenance of neurogenic inflammation contributes to a vicious cycle in skin. Exp Dermatol 24(10):723–726.  https://doi.org/10.1111/exd.12798 PubMedCrossRefGoogle Scholar
  43. 43.
    Mollanazar NK, Smith PK, Yosipovitch G (2016) Mediators of chronic pruritus in atopic dermatitis: getting the itch out? Clin Rev Allergy Immunol 51(3):263–292.  https://doi.org/10.1007/s12016-015-8488-5 PubMedCrossRefGoogle Scholar
  44. 44.
    Briot A, Deraison C, Lacroix M, Bonnart C, Robin A, Besson C, Dubus P, Hovnanian A (2009) Kallikrein 5 induces atopic dermatitis-like lesions through PAR2-mediated thymic stromal lymphopoietin expression in Netherton syndrome. J Exp Med 206(5):1135–1147.  https://doi.org/10.1084/jem.20082242 PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Tourdot BE, Conaway S, Niisuke K, Edelstein LC, Bray PF, Holinstat M (2014) Mechanism of race-dependent platelet activation through the protease-activated receptor-4 and Gq signaling axis. Arterioscler Thromb Vasc Biol 34(12):2644–2650.  https://doi.org/10.1161/atvbaha.114.304249 PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Vellani V, Kinsey AM, Prandini M, Hechtfischer SC, Reeh P, Magherini PC, Giacomoni C, McNaughton PA (2010) Protease activated receptors 1 and 4 sensitize TRPV1 in nociceptive neurones. Mol Pain 6:61.  https://doi.org/10.1186/1744-8069-6-61 PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Karanjia R, Spreadbury I, Bautista-Cruz F, Tsang ME, Vanner S (2009) Activation of protease-activated receptor-4 inhibits the intrinsic excitability of colonic dorsal root ganglia neurons. Neurogastroenterol Motil 21(11):1218–1221.  https://doi.org/10.1111/j.1365-2982.2009.01353.x PubMedCrossRefGoogle Scholar
  48. 48.
    Asfaha S, Cenac N, Houle S, Altier C, Papez MD, Nguyen C, Steinhoff M, Chapman K, Zamponi GW, Vergnolle N (2007) Protease-activated receptor-4: a novel mechanism of inflammatory pain modulation. Br J Pharmacol 150(2):176–185.  https://doi.org/10.1038/sj.bjp.0706975 PubMedCrossRefGoogle Scholar
  49. 49.
    Houle S, Papez MD, Ferazzini M, Hollenberg MD, Vergnolle N (2005) Neutrophils and the kallikrein-kinin system in proteinase-activated receptor 4-mediated inflammation in rodents. Br J Pharmacol 146(5):670–678.  https://doi.org/10.1038/sj.bjp.0706371 PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Liu Q, Tang Z, Surdenikova L, Kim S, Patel KN, Kim A, Ru F, Guan Y, Weng HJ, Geng Y, Undem BJ, Kollarik M, Chen ZF, Anderson DJ, Dong X (2009) Sensory neuron-specific GPCR Mrgprs are itch receptors mediating chloroquine-induced pruritus. Cell 139(7):1353–1365.  https://doi.org/10.1016/j.cell.2009.11.034 PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Wilson SR, Gerhold KA, Bifolck-Fisher A, Liu Q, Patel KN, Dong X, Bautista DM (2011) TRPA1 is required for histamine-independent, Mas-related G protein-coupled receptor-mediated itch. Nat Neurosci 14(5):595–602.  https://doi.org/10.1038/nn.2789 PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Solinski HJ, Gudermann T, Breit A (2014) Pharmacology and signaling of MAS-related G protein-coupled receptors. Pharmacol Rev 66(3):570–597.  https://doi.org/10.1124/pr.113.008425 PubMedCrossRefGoogle Scholar
  53. 53.
    Bader M, Alenina N, Andrade-Navarro MA, Santos RA (2014) MAS and its related G protein-coupled receptors, Mrgprs. Pharmacol Rev 66(4):1080–1105.  https://doi.org/10.1124/pr.113.008136 PubMedCrossRefGoogle Scholar
  54. 54.
    Solinski HJ, Petermann F, Rothe K, Boekhoff I, Gudermann T, Breit A (2013) Human Mas-related G protein-coupled receptors-X1 induce chemokine receptor 2 expression in rat dorsal root ganglia neurons and release of chemokine ligand 2 from the human LAD-2 mast cell line. PLoS One 8(3):e58756.  https://doi.org/10.1371/journal.pone.0058756 PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Boillat A, Alijevic O, Kellenberger S (2014) Calcium entry via TRPV1 but not ASICs induces neuropeptide release from sensory neurons. Mol Cell Neurosci 61:13–22.  https://doi.org/10.1016/j.mcn.2014.04.007 PubMedCrossRefGoogle Scholar
  56. 56.
    Stander S, Moormann C, Schumacher M, Buddenkotte J, Artuc M, Shpacovitch V, Brzoska T, Lippert U, Henz BM, Luger TA, Metze D, Steinhoff M (2004) Expression of vanilloid receptor subtype 1 in cutaneous sensory nerve fibers, mast cells, and epithelial cells of appendage structures. Exp Dermatol 13(3):129–139.  https://doi.org/10.1111/j.0906-6705.2004.0178.x PubMedCrossRefGoogle Scholar
  57. 57.
    Story GM, Peier AM, Reeve AJ, Eid SR, Mosbacher J, Hricik TR, Earley TJ, Hergarden AC, Andersson DA, Hwang SW, McIntyre P, Jegla T, Bevan S, Patapoutian A (2003) ANKTM1, a TRP-like channel expressed in nociceptive neurons, is activated by cold temperatures. Cell 112(6):819–829PubMedCrossRefGoogle Scholar
  58. 58.
    Hojland CR, Andersen HH, Poulsen JN, Arendt-Nielsen L, Gazerani P (2015) A human surrogate model of itch utilizing the TRPA1 agonist trans-cinnamaldehyde. Acta Derm Venereol 95(7):798–803.  https://doi.org/10.2340/00015555-2103 PubMedCrossRefGoogle Scholar
  59. 59.
    Liang J, Ji Q, Ji W (2011) Role of transient receptor potential ankyrin subfamily member 1 in pruritus induced by endothelin-1. Neurosci Lett 492(3):175–178.  https://doi.org/10.1016/j.neulet.2011.02.009 PubMedCrossRefGoogle Scholar
  60. 60.
    Liu T, Xu ZZ, Park CK, Berta T, Ji RR (2010) Toll-like receptor 7 mediates pruritus. Nat Neurosci 13(12):1460–1462.  https://doi.org/10.1038/nn.2683 PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Kim SJ, Park GH, Kim D, Lee J, Min H, Wall E, Lee CJ, Simon MI, Lee SJ, Han SK (2011) Analysis of cellular and behavioral responses to imiquimod reveals a unique itch pathway in transient receptor potential vanilloid 1 (TRPV1)-expressing neurons. Proc Natl Acad Sci U S A 108(8):3371–3376.  https://doi.org/10.1073/pnas.1019755108 PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Yun JW, Seo JA, Jeong YS, Bae IH, Jang WH, Lee J, Kim SY, Shin SS, Woo BY, Lee KW, Lim KM, Park YH (2011) TRPV1 antagonist can suppress the atopic dermatitis-like symptoms by accelerating skin barrier recovery. J Dermatol Sci 62(1):8–15.  https://doi.org/10.1016/j.jdermsci.2010.10.014 PubMedCrossRefGoogle Scholar
  63. 63.
    Dai Y, Wang S, Tominaga M, Yamamoto S, Fukuoka T, Higashi T, Kobayashi K, Obata K, Yamanaka H, Noguchi K (2007) Sensitization of TRPA1 by PAR2 contributes to the sensation of inflammatory pain. J Clin Invest 117(7):1979–1987.  https://doi.org/10.1172/jci30951 PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Malin S, Molliver D, Christianson JA, Schwartz ES, Cornuet P, Albers KM, Davis BM (2011) TRPV1 and TRPA1 function and modulation are target tissue dependent. J Neurosci 31(29):10516–10528.  https://doi.org/10.1523/jneurosci.2992-10.2011 PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Wang S, Dai Y, Fukuoka T, Yamanaka H, Kobayashi K, Obata K, Cui X, Tominaga M, Noguchi K (2008) Phospholipase C and protein kinase A mediate bradykinin sensitization of TRPA1: a molecular mechanism of inflammatory pain. Brain 131(5):1241–1251.  https://doi.org/10.1093/brain/awn060 PubMedCrossRefGoogle Scholar
  66. 66.
    Wilson SR, The L, Batia LM, Beattie K, Katibah GE, McClain SP, Pellegrino M, Estandian DM, Bautista DM (2013) The epithelial cell-derived atopic dermatitis cytokine TSLP activates neurons to induce itch. Cell 155(2):285–295.  https://doi.org/10.1016/j.cell.2013.08.057 PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Oh MH, Oh SY, Lu J, Lou H, Myers AC, Zhu Z, Zheng T (2013) TRPA1-dependent pruritus in IL-13-induced chronic atopic dermatitis. J Immunol (Baltimore, Md : 1950) 191(11):5371–5382.  https://doi.org/10.4049/jimmunol.1300300 CrossRefGoogle Scholar
  68. 68.
    Bautista DM, Pellegrino M, Tsunozaki M (2013) TRPA1: a gatekeeper for inflammation. Annu Rev Physiol 75:181–200.  https://doi.org/10.1146/annurev-physiol-030212-183811 PubMedCrossRefGoogle Scholar
  69. 69.
    Gouin O, L'Herondelle K, Lebonvallet N, Le Gall-Ianotto C, Sakka M, Buhe V, Plee-Gautier E, Carre JL, Lefeuvre L, Misery L, Le Garrec R (2017) TRPV1 and TRPA1 in cutaneous neurogenic and chronic inflammation: pro-inflammatory response induced by their activation and their sensitization. Protein Cell.  https://doi.org/10.1007/s13238-017-0395-5
  70. 70.
    Kodji X, Aubdool AA, Brain SD (2016) Evidence for physiological and pathological roles for sensory nerves in the microvasculature and skin. Curr Res Transl Med 64(4):195–201.  https://doi.org/10.1016/j.retram.2016.09.002 PubMedCrossRefGoogle Scholar
  71. 71.
    Two AM, Wu W, Gallo RL, Hata TR (2015) Rosacea: part I. Introduction, categorization, histology, pathogenesis, and risk factors. J Am Acad Dermatol 72(5):749–758; quiz 759-760.  https://doi.org/10.1016/j.jaad.2014.08.028 PubMedCrossRefGoogle Scholar
  72. 72.
    Guzman-Sanchez DA, Ishiuji Y, Patel T, Fountain J, Chan YH, Yosipovitch G (2007) Enhanced skin blood flow and sensitivity to noxious heat stimuli in papulopustular rosacea. J Am Acad Dermatol 57(5):800–805.  https://doi.org/10.1016/j.jaad.2007.06.009 PubMedCrossRefGoogle Scholar
  73. 73.
    Schwab VD, Sulk M, Seeliger S, Nowak P, Aubert J, Mess C, Rivier M, Carlavan I, Rossio P, Metze D, Buddenkotte J, Cevikbas F, Voegel JJ, Steinhoff M (2011) Neurovascular and neuroimmune aspects in the pathophysiology of rosacea. J Investig Dermatol Symp Proc 15(1):53–62.  https://doi.org/10.1038/jidsymp.2011.6 PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Sulk M, Seeliger S, Aubert J, Schwab VD, Cevikbas F, Rivier M, Nowak P, Voegel JJ, Buddenkotte J, Steinhoff M (2012) Distribution and expression of non-neuronal transient receptor potential (TRPV) ion channels in rosacea. J Investig Dermatol 132(4):1253–1262.  https://doi.org/10.1038/jid.2011.424 PubMedCrossRefGoogle Scholar
  75. 75.
    Gerber PA, Buhren BA, Steinhoff M, Homey B (2011) Rosacea: the cytokine and chemokine network. J Investig Dermatol Symp Proc 15(1):40–47.  https://doi.org/10.1038/jidsymp.2011.9 PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Ni Raghallaigh S, Powell FC (2014) Epidermal hydration levels in patients with rosacea improve after minocycline therapy. Br J Dermatol 171(2):259–266.  https://doi.org/10.1111/bjd.12770 PubMedCrossRefGoogle Scholar
  77. 77.
    Hachem JP, Houben E, Crumrine D, Man MQ, Schurer N, Roelandt T, Choi EH, Uchida Y, Brown BE, Feingold KR, Elias PM (2006) Serine protease signaling of epidermal permeability barrier homeostasis. J Investig Dermatol 126(9):2074–2086.  https://doi.org/10.1038/sj.jid.5700351 PubMedCrossRefGoogle Scholar
  78. 78.
    Spoendlin J, Voegel JJ, Jick SS, Meier CR (2013) Risk of rosacea in patients with diabetes using insulin or oral antidiabetic drugs. J Investig Dermatol 133(12):2790–2793.  https://doi.org/10.1038/jid.2013.225 PubMedCrossRefGoogle Scholar
  79. 79.
    Pozsgai G, Bodkin JV, Graepel R, Bevan S, Andersson DA, Brain SD (2010) Evidence for the pathophysiological relevance of TRPA1 receptors in the cardiovascular system in vivo. Cardiovasc Res 87(4):760–768.  https://doi.org/10.1093/cvr/cvq118 PubMedCrossRefGoogle Scholar
  80. 80.
    Graepel R, Fernandes ES, Aubdool AA, Andersson DA, Bevan S, Brain SD (2011) 4-oxo-2-nonenal (4-ONE): evidence of transient receptor potential ankyrin 1-dependent and -independent nociceptive and vasoactive responses in vivo. J Pharmacol Exp Ther 337(1):117–124.  https://doi.org/10.1124/jpet.110.172403 PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Baylie RL, Brayden JE (2011) TRPV channels and vascular function. Acta Physiol (Oxford, England) 203(1):99–116.  https://doi.org/10.1111/j.1748-1716.2010.02217.x CrossRefGoogle Scholar
  82. 82.
    Helfrich YR, Maier LE, Cui Y, Fisher GJ, Chubb H, Fligiel S, Sachs D, Varani J, Voorhees J (2015) Clinical, histologic, and molecular analysis of differences between erythematotelangiectatic rosacea and telangiectatic photoaging. JAMA Dermatol 151(8):825–836.  https://doi.org/10.1001/jamadermatol.2014.4728 PubMedCrossRefGoogle Scholar
  83. 83.
    Greeno EW, Mantyh P, Vercellotti GM, Moldow CF (1993) Functional neurokinin 1 receptors for substance P are expressed by human vascular endothelium. J Exp Med 177(5):1269–1276PubMedCrossRefGoogle Scholar
  84. 84.
    Seeliger S, Buddenkotte J, Schmidt-Choudhury A, Rosignoli C, Shpacovitch V, von Arnim U, Metze D, Rukwied R, Schmelz M, Paus R, Voegel JJ, Schmidt WE, Steinhoff M (2010) Pituitary adenylate cyclase activating polypeptide: an important vascular regulator in human skin in vivo. Am J Pathol 177(5):2563–2575.  https://doi.org/10.2353/ajpath.2010.090941 PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    Muto Y, Wang Z, Vanderberghe M, Two A, Gallo RL, Di Nardo A (2014) Mast cells are key mediators of cathelicidin-initiated skin inflammation in rosacea. J Investig Dermatol 134(11):2728–2736.  https://doi.org/10.1038/jid.2014.222 PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    Madva EN, Granstein RD (2013) Nerve-derived transmitters including peptides influence cutaneous immunology. Brain Behav Immun 34:1–10.  https://doi.org/10.1016/j.bbi.2013.03.006 PubMedCrossRefGoogle Scholar
  87. 87.
    Shi X, Wang L, Li X, Sahbaie P, Kingery WS, Clark JD (2011) Neuropeptides contribute to peripheral nociceptive sensitization by regulating interleukin-1beta production in keratinocytes. Anesth Analg 113(1):175–183.  https://doi.org/10.1213/ANE.0b013e31821a0258 PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    Park KY, Hyun MY, Jeong SY, Kim BJ, Kim MN, Hong CK (2015) Botulinum toxin for the treatment of refractory erythema and flushing of rosacea. Dermatology (Basel, Switzerland) 230(4):299–301.  https://doi.org/10.1159/000368773 CrossRefGoogle Scholar
  89. 89.
    Michalek IM, Loring B, John SM (2017) A systematic review of worldwide epidemiology of psoriasis. J Eur Acad Dermatol Venereol JEADV 31(2):205–212.  https://doi.org/10.1111/jdv.13854 PubMedCrossRefGoogle Scholar
  90. 90.
    Di Cesare A, Di Meglio P, Nestle FO (2009) The IL-23/Th17 axis in the immunopathogenesis of psoriasis. J Investig Dermatol 129(6):1339–1350.  https://doi.org/10.1038/jid.2009.59 PubMedCrossRefGoogle Scholar
  91. 91.
    Veale D, Farrell M, Fitzgerald O (1993) Mechanism of joint sparing in a patient with unilateral psoriatic arthritis and a longstanding hemiplegia. Br J Rheumatol 32(5):413–416PubMedCrossRefGoogle Scholar
  92. 92.
    Sowell JK, Pippenger MA, Crowe MJ (1993) Psoriasis contralateral to hemiparesis following cerebrovascular accident. Int J Dermatol 32(8):598–599PubMedCrossRefGoogle Scholar
  93. 93.
    Sethi S, Sequeira W (1990) Sparing effect of hemiplegia on scleroderma. Ann Rheum Dis 49(12):999–1000PubMedPubMedCentralCrossRefGoogle Scholar
  94. 94.
    Joseph T, Kurian J, Warwick DJ, Friedmann PS (2005) Unilateral remission of psoriasis following traumatic nerve palsy. Br J Dermatol 152(1):185–186.  https://doi.org/10.1111/j.1365-2133.2005.06330.x PubMedCrossRefGoogle Scholar
  95. 95.
    Farber EM, Lanigan SW, Boer J (1990) The role of cutaneous sensory nerves in the maintenance of psoriasis. Int J Dermatol 29(6):418–420PubMedCrossRefGoogle Scholar
  96. 96.
    Raychaudhuri SP, Farber EM (1993) Are sensory nerves essential for the development of psoriatic lesions? J Am Acad Dermatol 28(3):488–489PubMedCrossRefGoogle Scholar
  97. 97.
    Dewing SB (1971) Remission of psoriasis associated with cutaneous nerve section. Arch Dermatol 104(2):220–221PubMedCrossRefGoogle Scholar
  98. 98.
    Reyter I, Woodley D (2004) Widespread unilateral plaques in a 68-year-old woman after neurosurgery. Arch Dermatol 140(12):1531–1536.  https://doi.org/10.1001/archderm.140.12.1531-e PubMedCrossRefGoogle Scholar
  99. 99.
    Chowdhury MM, Hedges R, Lanigan SW (2000) Unilateral resolution of palmar eczema and hyperhidrosis complicated by Horner's syndrome following ipsilateral endoscopic cervical sympathectomy. Br J Dermatol 143(3):653–654PubMedCrossRefGoogle Scholar
  100. 100.
    Ostrowski SM, Belkadi A, Loyd CM, Diaconu D, Ward NL (2011) Cutaneous denervation of psoriasiform mouse skin improves acanthosis and inflammation in a sensory neuropeptide-dependent manner. J Investig Dermatol 131(7):1530–1538.  https://doi.org/10.1038/jid.2011.60 PubMedPubMedCentralCrossRefGoogle Scholar
  101. 101.
    Saraceno R, Kleyn CE, Terenghi G, Griffiths CE (2006) The role of neuropeptides in psoriasis. Br J Dermatol 155(5):876–882.  https://doi.org/10.1111/j.1365-2133.2006.07518.x PubMedCrossRefGoogle Scholar
  102. 102.
    Payan DG, Brewster DR, Goetzl EJ (1983) Specific stimulation of human T lymphocytes by substance P. J Immunol (Baltimore, Md : 1950) 131(4):1613–1615Google Scholar
  103. 103.
    Maggi CA (1997) The effects of tachykinins on inflammatory and immune cells. Regul Pept 70(2–3):75–90PubMedCrossRefGoogle Scholar
  104. 104.
    O'Halloran DJ, Bloom SR (1991) Calcitonin gene related peptide. BMJ (Clinical research ed) 302(6779):739–740CrossRefGoogle Scholar
  105. 105.
    Kakurai M, Fujita N, Murata S, Furukawa Y, Demitsu T, Nakagawa H (2001) Vasoactive intestinal peptide regulates its receptor expression and functions of human keratinocytes via type I vasoactive intestinal peptide receptors. J Investig Dermatol 116(5):743–749.  https://doi.org/10.1046/j.0022-202x.2001.doc.x PubMedCrossRefGoogle Scholar
  106. 106.
    Amatya B, Wennersten G, Nordlind K (2008) Patients’ perspective of pruritus in chronic plaque psoriasis: a questionnaire-based study. J Eur Acad Dermatol Venereol JEADV 22(7):822–826.  https://doi.org/10.1111/j.1468-3083.2008.02591.x PubMedCrossRefGoogle Scholar
  107. 107.
    Amatya B, El-Nour H, Holst M, Theodorsson E, Nordlind K (2011) Expression of tachykinins and their receptors in plaque psoriasis with pruritus. Br J Dermatol 164(5):1023–1029.  https://doi.org/10.1111/j.1365-2133.2011.10241.x PubMedCrossRefGoogle Scholar
  108. 108.
    Chang SE, Han SS, Jung HJ, Choi JH (2007) Neuropeptides and their receptors in psoriatic skin in relation to pruritus. Br J Dermatol 156(6):1272–1277.  https://doi.org/10.1111/j.1365-2133.2007.07935.x PubMedCrossRefGoogle Scholar
  109. 109.
    Nakamura M, Toyoda M, Morohashi M (2003) Pruritogenic mediators in psoriasis vulgaris: comparative evaluation of itch-associated cutaneous factors. Br J Dermatol 149(4):718–730PubMedCrossRefGoogle Scholar
  110. 110.
    Raychaudhuri SK, Raychaudhuri SP, Weltman H, Farber EM (2001) Effect of nerve growth factor on endothelial cell biology: proliferation and adherence molecule expression on human dermal microvascular endothelial cells. Arch Dermatol Res 293(6):291–295PubMedCrossRefGoogle Scholar
  111. 111.
    Bischoff SC, Dahinden CA (1992) Effect of nerve growth factor on the release of inflammatory mediators by mature human basophils. Blood 79(10):2662–2669PubMedGoogle Scholar
  112. 112.
    Taneda K, Tominaga M, Negi O, Tengara S, Kamo A, Ogawa H, Takamori K (2011) Evaluation of epidermal nerve density and opioid receptor levels in psoriatic itch. Br J Dermatol 165(2):277–284.  https://doi.org/10.1111/j.1365-2133.2011.10347.x PubMedCrossRefGoogle Scholar
  113. 113.
    Kou K, Nakamura F, Aihara M, Chen H, Seto K, Komori-Yamaguchi J, Kambara T, Nagashima Y, Goshima Y, Ikezawa Z (2012) Decreased expression of semaphorin-3A, a neurite-collapsing factor, is associated with itch in psoriatic skin. Acta Derm Venereol 92(5):521–528.  https://doi.org/10.2340/00015555-1350 PubMedCrossRefGoogle Scholar
  114. 114.
    Zanchi M, Favot F, Bizzarini M, Piai M, Donini M, Sedona P (2008) Botulinum toxin type-A for the treatment of inverse psoriasis. J Eur Acad Dermatol Venereol JEADV 22(4):431–436.  https://doi.org/10.1111/j.1468-3083.2007.02457.x PubMedCrossRefGoogle Scholar
  115. 115.
    Ward NL, Kavlick KD, Diaconu D, Dawes SM, Michaels KA, Gilbert E (2012) Botulinum neurotoxin A decreases infiltrating cutaneous lymphocytes and improves acanthosis in the KC-Tie2 mouse model. J Investig Dermatol 132(7):1927–1930.  https://doi.org/10.1038/jid.2012.60 PubMedPubMedCentralCrossRefGoogle Scholar
  116. 116.
    Todberg T, Zachariae C, Bregnhoj A, Hedelund L, Bonefeld KK, Nielsen K, Iversen L, Skov L (2017) The effect of botulinum neurotoxin A in patients with plaque psoriasis—an exploratory trial. J Eur Acad Dermatol Venereol JEADV 32:e81–e82.  https://doi.org/10.1111/jdv.14536 PubMedCrossRefGoogle Scholar
  117. 117.
    Leung DY, Bieber T (2003) Atopic dermatitis. Lancet (London, England) 361(9352):151–160.  https://doi.org/10.1016/s0140-6736(03)12193-9 CrossRefGoogle Scholar
  118. 118.
    Tominaga M, Tengara S, Kamo A, Ogawa H, Takamori K (2009) Psoralen-ultraviolet A therapy alters epidermal Sema3A and NGF levels and modulates epidermal innervation in atopic dermatitis. J Dermatol Sci 55(1):40–46.  https://doi.org/10.1016/j.jdermsci.2009.03.007 PubMedCrossRefGoogle Scholar
  119. 119.
    Dou YC, Hagstromer L, Emtestam L, Johansson O (2006) Increased nerve growth factor and its receptors in atopic dermatitis: an immunohistochemical study. Arch Dermatol Res 298(1):31–37.  https://doi.org/10.1007/s00403-006-0657-1 PubMedCrossRefGoogle Scholar
  120. 120.
    Jarvikallio A, Harvima IT, Naukkarinen A (2003) Mast cells, nerves and neuropeptides in atopic dermatitis and nummular eczema. Arch Dermatol Res 295(1):2–7.  https://doi.org/10.1007/s00403-002-0378-z PubMedCrossRefGoogle Scholar
  121. 121.
    Tobin D, Nabarro G, Baart de la Faille H, van Vloten WA, van der Putte SC, Schuurman HJ (1992) Increased number of immunoreactive nerve fibers in atopic dermatitis. J Allergy Clin Immunol 90(4 Pt 1):613–622PubMedCrossRefGoogle Scholar
  122. 122.
    Ostlere LS, Cowen T, Rustin MH (1995) Neuropeptides in the skin of patients with atopic dermatitis. Clin Exp Dermatol 20(6):462–467PubMedCrossRefGoogle Scholar
  123. 123.
    Roggenkamp D, Falkner S, Stab F, Petersen M, Schmelz M, Neufang G (2012) Atopic keratinocytes induce increased neurite outgrowth in a coculture model of porcine dorsal root ganglia neurons and human skin cells. J Investig Dermatol 132(7):1892–1900.  https://doi.org/10.1038/jid.2012.44 PubMedCrossRefGoogle Scholar
  124. 124.
    Yamaguchi J, Aihara M, Kobayashi Y, Kambara T, Ikezawa Z (2009) Quantitative analysis of nerve growth factor (NGF) in the atopic dermatitis and psoriasis horny layer and effect of treatment on NGF in atopic dermatitis. J Dermatol Sci 53(1):48–54.  https://doi.org/10.1016/j.jdermsci.2008.08.011 PubMedCrossRefGoogle Scholar
  125. 125.
    Takano N, Sakurai T, Ohashi Y, Kurachi M (2007) Effects of high-affinity nerve growth factor receptor inhibitors on symptoms in the NC/Nga mouse atopic dermatitis model. Br J Dermatol 156(2):241–246.  https://doi.org/10.1111/j.1365-2133.2006.07636.x PubMedCrossRefGoogle Scholar
  126. 126.
    Grewe M, Vogelsang K, Ruzicka T, Stege H, Krutmann J (2000) Neurotrophin-4 production by human epidermal keratinocytes: increased expression in atopic dermatitis. J Investig Dermatol 114(6):1108–1112.  https://doi.org/10.1046/j.1523-1747.2000.00974.x PubMedCrossRefGoogle Scholar
  127. 127.
    Tominaga M, Ogawa H, Takamori K (2008) Decreased production of semaphorin 3A in the lesional skin of atopic dermatitis. Br J Dermatol 158(4):842–844.  https://doi.org/10.1111/j.1365-2133.2007.08410.x PubMedCrossRefGoogle Scholar
  128. 128.
    Kinkelin I, Motzing S, Koltenzenburg M, Brocker EB (2000) Increase in NGF content and nerve fiber sprouting in human allergic contact eczema. Cell Tissue Res 302(1):31–37PubMedCrossRefGoogle Scholar
  129. 129.
    Salomon J, Baran E (2008) The role of selected neuropeptides in pathogenesis of atopic dermatitis. J Eur Acad Dermatol Venereol JEADV 22(2):223–228.  https://doi.org/10.1111/j.1468-3083.2007.02399.x PubMedCrossRefGoogle Scholar
  130. 130.
    Kim KH, Park KC, Chung JH, Choi HR (2003) The effect of substance P on peripheral blood mononuclear cells in patients with atopic dermatitis. J Dermatol Sci 32(2):115–124PubMedCrossRefGoogle Scholar
  131. 131.
    Gordon DJ, Ostlere LS, Holden CA (1997) Neuropeptide modulation of Th1 and Th2 cytokines in peripheral blood mononuclear leucocytes in atopic dermatitis and non-atopic controls. Br J Dermatol 137(6):921–927PubMedCrossRefGoogle Scholar
  132. 132.
    Antunez C, Torres MJ, Lopez S, Rodriguez-Pena R, Blanca M, Mayorga C, Santamaria-Babi LF (2009) Calcitonin gene-related peptide modulates interleukin-13 in circulating cutaneous lymphocyte-associated antigen-positive T cells in patients with atopic dermatitis. Br J Dermatol 161(3):547–553.  https://doi.org/10.1111/j.1365-2133.2009.09318.x PubMedCrossRefGoogle Scholar
  133. 133.
    Pavlovic S, Daniltchenko M, Tobin DJ, Hagen E, Hunt SP, Klapp BF, Arck PC, Peters EM (2008) Further exploring the brain-skin connection: stress worsens dermatitis via substance P-dependent neurogenic inflammation in mice. J Investig Dermatol 128(2):434–446.  https://doi.org/10.1038/sj.jid.5701079 PubMedCrossRefGoogle Scholar
  134. 134.
    Scholzen T, Armstrong CA, Bunnett NW, Luger TA, Olerud JE, Ansel JC (1998) Neuropeptides in the skin: interactions between the neuroendocrine and the skin immune systems. Exp Dermatol 7(2–3):81–96PubMedCrossRefGoogle Scholar
  135. 135.
    Andoh T, Nagasawa T, Satoh M, Kuraishi Y (1998) Substance P induction of itch-associated response mediated by cutaneous NK1 tachykinin receptors in mice. J Pharmacol Exp Ther 286(3):1140–1145PubMedGoogle Scholar
  136. 136.
    Ohmura T, Hayashi T, Satoh Y, Konomi A, Jung B, Satoh H (2004) Involvement of substance P in scratching behaviour in an atopic dermatitis model. Eur J Pharmacol 491(2–3):191–194.  https://doi.org/10.1016/j.ejphar.2004.03.047 PubMedCrossRefGoogle Scholar
  137. 137.
    Dando TM, Perry CM (2004) Aprepitant: a review of its use in the prevention of chemotherapy-induced nausea and vomiting. Drugs 64(7):777–794PubMedCrossRefGoogle Scholar
  138. 138.
    Duval A, Dubertret L (2009) Aprepitant as an antipruritic agent? N Engl J Med 361(14):1415–1416.  https://doi.org/10.1056/NEJMc0906670 PubMedCrossRefGoogle Scholar
  139. 139.
    Lee JH, Cho SH (2011) Korean red ginseng extract ameliorates skin lesions in NC/Nga mice: an atopic dermatitis model. J Ethnopharmacol 133(2):810–817.  https://doi.org/10.1016/j.jep.2010.11.020 PubMedCrossRefGoogle Scholar
  140. 140.
    Liu B, Escalera J, Balakrishna S, Fan L, Caceres AI, Robinson E, Sui A, McKay MC, McAlexander MA, Herrick CA, Jordt SE (2013) TRPA1 controls inflammation and pruritogen responses in allergic contact dermatitis. FASEB J 27(9):3549–3563.  https://doi.org/10.1096/fj.13-229948 PubMedPubMedCentralCrossRefGoogle Scholar
  141. 141.
    Doyle JA, Connolly SM, Hunziker N, Winkelmann RK (1979) Prurigo nodularis: a reappraisal of the clinical and histologic features. J Cutan Pathol 6(5):392–403PubMedCrossRefGoogle Scholar
  142. 142.
    Cowan MA (1964) Neurohistological changes in prurigo nodularis. Arch Dermatol 89:754–758PubMedCrossRefGoogle Scholar
  143. 143.
    Johansson O, Liang Y, Emtestam L (2002) Increased nerve growth factor- and tyrosine kinase A-like immunoreactivities in prurigo nodularis skin—an exploration of the cause of neurohyperplasia. Arch Dermatol Res 293(12):614–619.  https://doi.org/10.1007/s00403-001-0285-8 PubMedCrossRefGoogle Scholar
  144. 144.
    Liang Y, Jacobi HH, Reimert CM, Haak-Frendscho M, Marcusson JA, Johansson O (2000) CGRP-immunoreactive nerves in prurigo nodularis—an exploration of neurogenic inflammation. J Cutan Pathol 27(7):359–366PubMedCrossRefGoogle Scholar
  145. 145.
    Mascarenhas NL, Wang Z, Chang YL, Di Nardo A (2017) TRPV4 mediates mast cell activation in cathelicidin-induced rosacea inflammation. J Investig Dermatol 137(4):972–975.  https://doi.org/10.1016/j.jid.2016.10.046 PubMedCrossRefGoogle Scholar
  146. 146.
    Williams MR, Gallo RL (2017) Evidence that human skin microbiome dysbiosis promotes atopic dermatitis. J Investig Dermatol 137(12):2460–2461.  https://doi.org/10.1016/j.jid.2017.09.010 PubMedPubMedCentralCrossRefGoogle Scholar
  147. 147.
    Wang Z, Mascarenhas N, Eckmann L, Miyamoto Y, Sun X, Kawakami T, Di Nardo A (2017) Skin microbiome promotes mast cell maturation by triggering stem cell factor production in keratinocytes. J Allergy Clin Immunol 139(4):1205–1216 e1206.  https://doi.org/10.1016/j.jaci.2016.09.019 PubMedCrossRefGoogle Scholar
  148. 148.
    Igawa S, Di Nardo A (2017) Skin microbiome and mast cells. Transl Res 184(6):68–76Google Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of DermatologyUniversity of California San DiegoLa JollaUSA

Personalised recommendations