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Substance P Enhances Th17 Phenotype in Individuals with Generalized Anxiety Disorder: an Event Resistant to Glucocorticoid Inhibition

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Abstract

Our objective was to evaluate the effect of stress-related dose of substance P (SP) on the in vitro proliferation and cytokine production in polyclonally activated T cells from healthy individuals or individuals with generalized anxiety disorder (GAD). Our results demonstrated that cell cultures from GAD group proliferated less following T cell activation, as compared with control group. The addition of SP enhanced, while the glucocorticoid (GC) reduced, the proliferative response in activated cell cultures from healthy but not from GAD individuals. The cytokine profile in GAD individuals revealed Th1 and Th2 deficiencies were associated with dominate Th17 phenotype which was enhanced by SP. Differently from control, the production of Th17 cytokines in GAD individuals was not affected by GC. In conclusion, our results show that complex T cell functional dysregulation in GAD individuals is significantly amplified by SP. These immune abnormalities can have impact in increasing the susceptibility to infectious diseases and inflammatory/autoimmune disorders in anxious individuals.

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References

  1. Lazarczyk M, Matyja E, Lipkowski A. Substance P and its receptors—a potencial target for novel medicines in malignant brain tumour therapies (mini-review). Folia Neuropathol. 2007;45(3):99–107.

    CAS  PubMed  Google Scholar 

  2. O’Connor TM, O’Connell J, O’Brien D, Goode T, Bredin CP, Shanahan F. The role os substante P in inflammatory disease. J Cell Physiol. 2004;201:167–80.

    Article  PubMed  Google Scholar 

  3. Hokfelt T, Pernow B, Wahren J. Substance P: a Pioneer amongst neuropeptides. J Intern Med. 2001;249:27–40.

    Article  CAS  PubMed  Google Scholar 

  4. Zhang Y, Berger A, Milne CD, Paige CJ. Tachykinins in the immune system. Curr Drug Targets. 2006;7:1011–20.

    Article  CAS  PubMed  Google Scholar 

  5. Lai JP, Douglas SD, Ho WZ. Human lymphocytes express substance P and its receptor. J Neuroimmunol. 1998;86:80–6.

    Article  CAS  PubMed  Google Scholar 

  6. Marriott I, Bost KL. IL-4 and IFN-gamma up-regulate substance P receptor expression in murine peritoneal macrophages. J Immunol. 2000;165:182–91.

    CAS  PubMed  Google Scholar 

  7. Lighvani S, Huang X, Trivedi PP, Swanborg RH, Hazlett LD. Substance P regulates natural killer cell interferon-y production and resistance to Pseudomonas aeruginosa infection. Eur J Immunol. 2005;35:1567–75.

    Article  CAS  PubMed  Google Scholar 

  8. Laurenzi MA, Persson MA, Dalsgaard CJ, Haegerstrand A. The neuropeptide substance P stimulates production of interleukin 1 in human blood monocytes: activated cells are preferentially influenced by the neuropeptide. Scand J Immunol. 1990;31:529–33.

    Article  CAS  PubMed  Google Scholar 

  9. Gutcher I, Becher B. APC-derived cytokines and T cell polarization in autoimmune inflammation. J Clin Invest. 2007;117:1119–25.

    Article  CAS  PubMed  Google Scholar 

  10. Crozat K, Vivier E, Dalod M. Crosstalk between components of the innate immune system: promoting anti-microbial defenses and avoiding immunopathologies. Immunol Rev. 2009;227:129–49.

    Article  CAS  PubMed  Google Scholar 

  11. Ekkens MJ, Liu Z, Liu Q, Whitmire J, Xiao S, et al. The role of OX40 ligand interactions in the development of the Th2 response to the gastrointestinal nematode parasite Heligmosomoides polygyrus. J Immunol. 2003;170(1):384–93.

    CAS  PubMed  Google Scholar 

  12. Wilson NJ, Boniface K, Chan JR, McKenzie B, Blumenschein WM, et al. de Waal Malefyt R: Development, cytokine profile and function of human interleukin 17-producing helper T cells. Nat Immunol. 2007;8:950–7.

    Article  CAS  PubMed  Google Scholar 

  13. Andoh A, Takaya H, Makino J, Sato H, Bamba S, et al. Cooperation of interleukin-17 and interferon-gamma on chemokine secretion in human fetal intestinal epithelial cells. Clin Exp Immunol. 2001;125:56–63.

    Article  CAS  PubMed  Google Scholar 

  14. Jovanovic DV, Di Battista JA, Martel-Pelletier J, Jolicoeur FC, He Y, et al. IL-17 stimulates the production and expression of pro-inflammatory cytokines, IL-beta and TNF-alpha, by human macrophages. J Immunol. 1998;160:3513–21.

    CAS  PubMed  Google Scholar 

  15. Matsuzaki G, Umemura M. IL-17 as an effetor molecule of innate and acquired immunity against infections. Microbiol Immunonol. 2007;51:1139–47.

    CAS  Google Scholar 

  16. Mathers AR, Tckacheva OA, Janelsins BM, Shufesky WJ, Morelli AE, Larregina AT. In vivo signaling through the neurokinin 1 receptor favors transgene expression by langerhans cells and promotes generation of Th1- and Tc1-biased immune responses. J Immunol. 2007;178:7006–17.

    CAS  PubMed  Google Scholar 

  17. Lotz M, Vaughan JH, Carson DA. Effect of neuropeptides on production of inflammatory cytokines by human onocytes. Science. 1988;241:1218–21.

    Article  CAS  PubMed  Google Scholar 

  18. Herpfer I, Lieb K. Substance P receptor antagonists in psychiatry: rationale for development and therapeutic potential. CNS Drugs. 2005;19:275–93.

    Article  CAS  PubMed  Google Scholar 

  19. Khouzam HR. Anxiety disorders: guidelines for effective primary care. Part 1: diagnosis. Consultant. 2009;49(3):1–3.

    Google Scholar 

  20. Boscarino JA. Posttraumatic stress disorder and physical illness: results from clinical and epidemiologic studies. Ann N Y Acad Sci. 2004;1032:141–53.

    Article  PubMed  Google Scholar 

  21. Sareen J, Cox BJ, Clara I, Asmundson GJ. The relationship between anxiety disorders and physical disorders in the U.S. National Comorbidity Survey. Depress Anxiety. 2005;21:193–202.

    Article  PubMed  Google Scholar 

  22. Schneiderman N, Ironson G, Siegel SD. Stress and health: psychological, behavioral, and biological determinants. Annu Rev Clin Psychol. 2005;1:607–28.

    Article  PubMed  Google Scholar 

  23. Godbout JP, Glaser R. Stress-induced immune dysregulation: implications for wound healing, infectious disease and cancer. J Neuroimmune Pharm. 2006;1:421–7.

    Article  Google Scholar 

  24. Arranz L, Guayerbas N, De la Fuente M. Impairment of several immune functions in anxious women. J Psychosom Res. 2007;62(1):1–8.

    Article  PubMed  Google Scholar 

  25. Zhou FL, Zhang WG, Wei YC, Xu KL, Hui LY, et al. Impact of comorbid anxiety and depression on quality of life and cellular immunity changes in patients with digestive tract cancers. World J Gastroenterol. 2005;11(15):2313–8.

    PubMed  Google Scholar 

  26. Koh KB, Lee Y. Reduced anxiety level by therapeutic interventions and cell-mediated immunity in panic disorder patients. Psychother Psychosom. 2004;73(5):286–92.

    Article  PubMed  Google Scholar 

  27. Gill JM, Saligan L, Woods S, Page G. PTSD is associated with an excess of inflammatory immune activities. Perspect Psychiatr Care. 2009;45(4):262–77.

    Article  PubMed  Google Scholar 

  28. Wessa M, Rohleder N. Endocrine and inflammatory alterations inposttraumatic stress disorder. Expert Rev Endocrinol Metab. 2007;2:91–122.

    Article  CAS  Google Scholar 

  29. Lemieux A, Coe CL, Carnes M. Symptom severity predicts degree of T cell activation in adult women following childhood maltreatment. Brain Behav Immun. 2008;22(6):994–1003.

    Article  PubMed  Google Scholar 

  30. Wilson S, van der Kolk B, Burbridge J, Fisler R, Kradin R. Phenotype of blood lymphocytes in PTSD suggests chronic immune activation. Psychosomatics. 1999;40:222–5.

    CAS  PubMed  Google Scholar 

  31. Boscarino JA, Chang J. Higher abnormal leukocyte and lymphocyte counts 20 years after exposure to severe stress: research and clinical implications. Psychosom Med. 1999;61:378–86.

    CAS  PubMed  Google Scholar 

  32. Cohen IR, Schwartz M. Autoimmune maintenance and neuroprotection of the central nervous system. J Neuroimmunol. 1999;100:111–4.

    Article  CAS  PubMed  Google Scholar 

  33. Affleck G, Urrows S, Tennen H, Higgins P, Pav D, Aloisi R. A dual pathway model of daily stressor effects on rheumatoid arthritis. Ann Behav Med. 1997;19:161–70.

    Article  CAS  PubMed  Google Scholar 

  34. Kohn PM, Kantor L, DeCicco TL, Beck AT. The beck anxiety inventory-trait (BAIT): a measure of dispositional anxiety not contaminated by dispositional depression. J Person Assessm. 2008;90:499–506.

    Article  Google Scholar 

  35. Hamilton M. The assessment of anxiety states by rating. Br J Med Psychol. 1959;32:50–5.

    CAS  PubMed  Google Scholar 

  36. Spitzer RL, Williams JB, Gibbon M, First MB. The structured clinical interview for DSM-III-R (SCID). I: history, rationale, and description. Arch Gen Psychiatry. 1992;49(8):624–9.

    CAS  PubMed  Google Scholar 

  37. Kang D, Davidson RJ, Coe CL, Wheeler RE, Tomarken AJ, Erschler WB. Frontal brain asymmetry and immune function. Behav Neurosc. 1991;105:860–9.

    Article  CAS  Google Scholar 

  38. Lemieux AM, Coe CL. Abuse-related post-traumatic stress disorder: evidence of chronic neuroendocrine activation in women. Psychosom Med. 1995;57:105–15.

    CAS  PubMed  Google Scholar 

  39. Strauman TJ, Lemieux AM, Coe CL. Self-discrepancies and natural killer cell activity: immunological consequences of negative self-evaluation. J Personal Soc Psychol. 1993;64:1042–52.

    Article  CAS  Google Scholar 

  40. Strauman TJ, Woods TE, Schneider KL, Kwapil L, Coe CL. Self-regulatory cognition and immune reactivity: idiographic success and failure feedback effects on the natural killer cell. Brain Beh Imm. 1993;18:544–54.

    Article  Google Scholar 

  41. Lang K, Drell TL, Niggemann B, Zanker KS, Entschladen F. Neurotransmitters regulate the migration and cytotoxicity in natural killer cells. Immunol Lett. 2003;2003(90):165–72.

    Article  Google Scholar 

  42. Bastian P, Posch B, Lang K, Niggemann B, Zaenker KS, et al. Phosphatidylinositol 3-kinase in the G protein-coupled receptor-induced chemokinesis and chemotaxis of MDA-MB-468 breast carcinoma cells: a comparison with leukocytes. Mol Cancer Res. 2006;4:411–21.

    Article  CAS  PubMed  Google Scholar 

  43. Bastian P, Balcarek A, Altanis C, Strell C, Niggemann B, et al. The inhibitory effect of norepinephrine on the migration of ES-2 ovarian carcinoma cells involves a Rap1-dependent pathway. Cancer Lett. 2009;274:218–24.

    Article  CAS  PubMed  Google Scholar 

  44. Lang K, Drell TL, Lindecke A, Niggemann B, Kaltschmidt C, et al. Induction of a metastatogenic tumor cell type by neurotransmitters and its pharmacological inhibition by established drugs. Int J Cancer. 2004;112:231–8.

    Article  CAS  PubMed  Google Scholar 

  45. Franchimont D, Galon J, Gadina M, Visconti R, Zhou Y, et al. Inhibition of Th1 immune response by glucocorticoids: neurotransmitters selectively inhibits IL-12-induced Stat4 phosphorylation in T lymphocytes. J Immunol. 2000;164:1768–74.

    CAS  PubMed  Google Scholar 

  46. Agarwal SK, Marshall GD. Glucocorticoid-induced type 1/type 2 cytokine alterations in humans: a model for stress-related immune dysfunction. J Interferon Cytokine Res. 1998;18:1059–68.

    Article  CAS  PubMed  Google Scholar 

  47. Lambrecht BN, Germonpre PR, Everaert EG, Carro-Muino I, De Veerman M, et al. Endogenously produced substance P contributes to lymphocyte proliferation induced by dendritic cells and direct TCR ligation. Eur J Immunol. 1999;29:3815–25.

    Article  CAS  PubMed  Google Scholar 

  48. Nio DA, Moylan RN, Roche JK. Modulation of T lymphocyte function by neuropeptides: evidence for their role as local immunoregulatory elements. J Immunol. 1993;150:5281–8.

    CAS  PubMed  Google Scholar 

  49. Takkouche B, Regueira C, Gestal-Otero JJ. A cohort study of stress and the common cold. Epidemiology. 2001;12:345–9.

    Article  CAS  PubMed  Google Scholar 

  50. Aviles H, Johnson MT, Monroy FP. Effects of cold stress on spleen cell proliferation and cytokine production during chronic Toxoplasma gondii infection. Neuroimmunomodulation. 2004;11(2):93–102.

    Article  CAS  PubMed  Google Scholar 

  51. Cohen F, Kemeny ME, Kearney KA, Zegans LS, Neuhaus JM, Conant MA. Persistent stress as a predictor of genital herpes recurrence. Arch Intern Med. 1999;159:2430–6.

    Article  CAS  PubMed  Google Scholar 

  52. Ben-Eliyahu S. The promotion of tumor metastasis by surgery and tress: immunological basis and implications for psychoneuroimmunology. Brain Behav Immun. 2003;17 Suppl 1:S27–36.

    Article  CAS  PubMed  Google Scholar 

  53. Romagnani S. The Th1/Th2 paradigm. Immunol Today. 1997;18:263–6.

    Article  CAS  PubMed  Google Scholar 

  54. Scholzen TE, Steinhoff M, Sindrilaru A, Schwarz A, Bunnett NW, et al. Cutaneous allergic contact dermatitis responses are diminished in mice deficient in neurokinin 1 receptors and augmented by neurokinin 2 receptor blockage. FASEB J. 2004;18:1007–9.

    CAS  PubMed  Google Scholar 

  55. Akkoc T, de Koning PJ, Rückert B, Barlan I, Akdis M, Akdis CA. Increased activation-induced cell death of high IFN-gamma-producing T(H)1 cells as a mechanism of T(H)2 predominance in atopic diseases. J Allergy Clin Immunol. 2008;121(3):652–8.

    Article  CAS  PubMed  Google Scholar 

  56. O’Connor JC, André C, Wang Y, Lawson MA, Szegedi SS, et al. Interferon-gamma and tumor necrosis factor-alpha mediate the upregulation of indoleamine 2, 3-dioxygenase and the induction of depressive-like behavior in mice in response to bacillus Calmette-Guerin. J Neurosci. 2009;29:4200–9.

    Article  PubMed  Google Scholar 

  57. Dai H, Daí Z. The role of tryptophan catabolism in acquisition and effector function of memory T cells. Cur Opin Organ Transpl. 2008;13:31–5.

    Article  Google Scholar 

  58. Holsboer F. The corticosteroid receptor hypothesis of depression. Neuropsychopharmacology. 2000;23:477–501.

    Article  CAS  PubMed  Google Scholar 

  59. Arborelius L, Owens MJ, Plotsky PM, Nemeroff CB. The role of corticotropin-releasing factor in depression and anxiety disorders. J Endocrinol. 1999;160:1–12.

    Article  CAS  PubMed  Google Scholar 

  60. Poliak S, Mor F, Conlon P, Wong T, Ling N, et al. Stress and autoimmunity: the neuropeptides corticotrophin releasing factor and urocortin suppress encephalomyelitis via effects on both the hypothalamic-pituitary-adrenal axis the immune system. J Immunol. 1997;158:5751–6.

    CAS  PubMed  Google Scholar 

  61. Ashwell JD, Lu FW, Vacchio MS. Glucocorticoids in T cell development and function. Annu Rev Immunol. 2000;18:309.

    Article  CAS  PubMed  Google Scholar 

  62. Toh MC, Kawashima M, Zrioual S, Hot A, Miossec P. IL-17 inhibits human Th17 differentiation through IL-12 beta 2 downregulation. Cytokine. 2009;48:226–30.

    Article  CAS  PubMed  Google Scholar 

  63. Newcomb DC, Zhou W, Moore ML, Goleniewska K, Hershey GK, et al. A functional IL-13 receptor is expressed on polarized murine CD4+ Th17 cells and IL-13 signaling attenuates Th17 cytokine production. J Immunol. 2009;182:5317–21.

    Article  CAS  PubMed  Google Scholar 

  64. Costantino CM, Baecher-Allan CM, Hafler DA. Human regulatory T cells and autoimmunity. Eur J Immunol. 2008;38:921–4.

    Article  CAS  PubMed  Google Scholar 

  65. Vignali DA, Collison LW, Workman CJ. How regulatory T cells work. Nat Rev Immunol. 2008;8:523–32.

    Article  CAS  PubMed  Google Scholar 

  66. Maynard CL, Harrington LE, Janowski KM, Oliver JR, Zindl CL, et al. Regulatory T cells expressing interleukin 10 develop from Foxp3+ and Foxp3-precursor cells in the absence of interleukin 10. Nat Immunol. 2007;8:931–41.

    Article  CAS  PubMed  Google Scholar 

  67. Kitani A, Fuss I, Nakamura K, Kumaki F, Usui T, Strober W. Transforming growth factor (TGF)-beta1-producing regulatory T cells induce Smad-mediated interleukin 10 secretion that facilitates coordinated immunoregulatory activity and amelioration of TGF-beta1-mediated fibrosis. J Exp Med. 2003;198:1179–88.

    Article  CAS  PubMed  Google Scholar 

  68. Shevach EM. Mechanisms of Foxp3+ T regulatory cell-mediated suppression. Immunity. 2009;30:636–45.

    Article  CAS  PubMed  Google Scholar 

  69. Belkaid Y. Regulatory T cells and infection: a dangerous necessity. Nat Rev Immunol. 2007;7:875–88.

    Article  CAS  PubMed  Google Scholar 

  70. McGeachy MJ, Stephens LA, Anderton SM. Natural recovery and protection from autoimmune encephalomyelitis: contribution of CD4 + CD25+ regulatory T cells within the central nervous system. J Immunol. 2005;175:3025–32.

    CAS  PubMed  Google Scholar 

  71. Li MO, Flavell RA. Contextual regulation of inflammation: a duet by transforming growth factor-b and interleukin-10. Immunity. 2008;8:468–76.

    Article  Google Scholar 

  72. De Kloet CS, Vermetten E, Geuze E, Kavelaars E, Heijnen A, Westenberg CJ. Assessment of HPA-axis function in posttraumatic stress disorder: pharmacological and non-pharmacological challenge tests, a review. J Psychiatry Res. 2006;40(6):550–67.

    Article  Google Scholar 

  73. Burchill MA, Yang J, Vang KB, Farrar MA. Interleukin-2 receptor signaling in regulatory T cell development and homeostasis. Immunol Lett. 2007;114:1–8.

    CAS  PubMed  Google Scholar 

  74. Davidson TS, DiPaolo RJ, Andersson J, Shevach EM. Cutting edge: IL-2 is essential for TGF-beta-mediated induction of Foxp3+ T regulatory cells. J Immunol. 2007;178:4022–6.

    CAS  PubMed  Google Scholar 

  75. Horwitz DA, Zheng SG, Wang J, Gray JD. Critical role of IL-2 and TGF-beta in generation, function and stabilization of Foxp3 + CD4+ Treg. Eur J Immunol. 2008;38:912–5.

    Article  CAS  PubMed  Google Scholar 

  76. Yang XO, Nurieva R, Martinez GJ, Kang HS, Chung Y, et al. Molecular antagonism and plasticity of regulatory and inflammatory T cell programs. Immunity. 2008;29:44–56.

    Article  CAS  PubMed  Google Scholar 

  77. Osorio F, LeibundGut-Landmann S, Lochner M, Lahl K, Sparwasser T, Eberl G, et al. DC activated via dectin-1 convert Treg into IL-17 producers. Eur J Immunol. 2008;38:3274–81.

    Article  CAS  PubMed  Google Scholar 

  78. Nalbandian A, Crispin JC, Tsokos GC. Interleukin-17 and systemic lupus erytematosus: current concepts. Clin Exp Immunol. 2009;157(2):209–15.

    Article  CAS  PubMed  Google Scholar 

  79. Di Cesare A, Di Meglio P, Nestle PD. The IL-23/Th17 axis in the immunopathogenesis of psoriasis. J Invest Dermatol. 2009;129(6):1339–50.

    Article  PubMed  Google Scholar 

  80. Korn T. Pathophysiology of multiple sclerosis. J Neurol. 2008;255(S6):2–6.

    Article  CAS  PubMed  Google Scholar 

  81. Liu ZJ, Yadav PK, Su JL, Wang JS, Fei K. Potential role of Th17 cells in the pathogenesis of inflammatory bowel disease. World J Gastroenterol. 2009;15(46):5784–8.

    Article  CAS  PubMed  Google Scholar 

  82. von Känel R, Hepp U, Kraemer B, Traber R, Keel M, et al. Evidence for low-grade systemic proinflammatory activity in individuals with posttraumatic stress disorder. J Psych Res. 2007;41:744–52.

    Article  Google Scholar 

  83. Muller N, Schwarz MJ. Immunology in anxiety and depression. In: Kasper S, den Boer JA, Sitsen JMA, editors. Handbook of depression and anxiety. New York: Marcel Dekker; 2002. p. 267–88.

    Google Scholar 

  84. Sutherland AG, Alexander DA, Hutchison JD. Disturbance of pro-inflammatory cytokines in post-traumatic psychopathology. Cytokine. 2003;24:219–25.

    Article  CAS  PubMed  Google Scholar 

  85. Gill JM, Vythilingam M, Page G. Low cortisol, high DHEA, and high levels of TNF-a and IL-6 in women with PTSD. J Traum Stress. 2008;21(6):530–9.

    Article  Google Scholar 

  86. Siebenhaar F, Sharo AA, Peters EMJ, Sharova TY, Syska W, Mardarye AN, et al. Substance P as an immunomodulatory neuropeptide in a mouse model for autoimmune hair loss (Alopecia Areata). J Investig Dermatol. 2007;127:1489–97.

    Article  CAS  PubMed  Google Scholar 

  87. Hordinsky M, Ericson M. Autoimmunity: alopecia areata. J Investig Dermatol Symp Proc. 2004;9:73–8.

    Article  PubMed  Google Scholar 

  88. Tuncer LI, Alacam T, Oral B. Substance P expression is elevated in inflamed human periradicular tissue. J Endod. 2004;30:329–32.

    Article  PubMed  Google Scholar 

  89. Felten DL, Felten SY, Bellinger DL, Lorton D. Noradrenergic and peptidergic innervation of secondary lymphoid organs: role in experimental rheumatoid arthritis. Eur J Clin Invest. 1992;22 Suppl 1:37–41.

    CAS  PubMed  Google Scholar 

  90. Calcagni E, Elenkov I. Stress system activity, innate and T helper cytokines, and susceptibility to immune-related diseases. Ann NY Acad Sci. 2006;1069:62–76.

    Article  CAS  PubMed  Google Scholar 

  91. Grimsholm O, Rantapää-Dahlqvist S, Dalén T, Forsgren S. Observations favouring the occurrence of local production and marked effects of bombesin/gastrin-releasing peptide in the synovial tissue of the human knee joint—comparisons with substance P and the NK-1 receptor. Neuropeptides. 2008;42(2):133–45.

    Article  CAS  PubMed  Google Scholar 

  92. Rösler N, Reuner C, Geiger J, Rissler K, Cramer H. Cerebrospinal fluid levels of immunoreactive substance P and somatostatin in patients with multiple sclerosis and inflammatory CNS disease. Peptides. 1990;11(1):181–3.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Microbiology and Parasitology, Federal University of the State of Rio de Janeiro, Frei Caneca 94, 20.261-040, Rio de Janeiro, RJ, Brazil

    Priscila O. Barros, Thais B. Ferreira, Morgana M. M. Vieira, Carla Renata M. Almeida, Carlos Fernando Araújo-Lima, Renato G. Silva-Filho, Joana Hygino, Regis M. Andrade & Cleonice A. Bento

  2. Department of Microbiology, State University of Rio de Janeiro, Rio de Janeiro, Brazil

    Arnaldo F. Andrade

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  1. Priscila O. Barros
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  2. Thais B. Ferreira
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Correspondence to Cleonice A. Bento.

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This work was supported by Fundação de Amparo à Pesquisa Carlos Chagas Filho (FAPERJ).

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Barros, P.O., Ferreira, T.B., Vieira, M.M.M. et al. Substance P Enhances Th17 Phenotype in Individuals with Generalized Anxiety Disorder: an Event Resistant to Glucocorticoid Inhibition. J Clin Immunol 31, 51–59 (2011). https://doi.org/10.1007/s10875-010-9466-6

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