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Basophil-derived IL-4 plays versatile roles in immunity

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Abstract

Recent studies demonstrated that basophils play crucial and non-redundant roles in the immune system, in spite of the fact that they are the rarest granulocytes and represent less than 1 % of peripheral blood leukocytes. In response to various stimuli, basophils release effector molecules stored in their cytoplasmic granules, including chemical mediators and proteases, and also secrete cytokines and chemokines. In this review, we will focus on the physiological and pathological roles of basophil-derived IL-4. Basophils can readily produce large quantities of IL-4 and are therefore the important source of IL-4. Basophil-derived IL-4 has been shown to regulate other immune cells, including T cells, B cells, group 2 innate lymphoid cells, monocytes, and macrophages. It also acts on non-hematopoietic cells such as fibroblasts and endothelial cells. Those cells stimulated with basophil-derived IL-4 contribute to the positive or negative regulation of a variety of immune responses in health and disease, including protection against parasitic and bacterial infections, allergy, and autoimmune diseases. Thus, basophil-derived IL-4 plays versatile roles in immunity.

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References

  1. Galli SJ (2000) Mast cells and basophils. Curr Opin Hematol 7:32–39

    Article  CAS  PubMed  Google Scholar 

  2. Seder RA, Paul WE, Dvorak AM, Sharkis SJ, Kagey-Sobotka A, Niv Y, Finkelman FD, Barbieri SA, Galli SJ, Plaut M (1991) Mouse splenic and bone marrow cell populations that express high-affinity Fc epsilon receptors and produce interleukin 4 are highly enriched in basophils. Proc Natl Acad Sci U S A 88:2835–2839

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Piccinni MP, Macchia D, Parronchi P, Giudizi MG, Bani D, Alterini R, Grossi A, Ricci M, Maggi E, Romagnani S (1991) Human bone marrow non-B, non-T cells produce interleukin 4 in response to cross-linkage of Fc epsilon and Fc gamma receptors. Proc Natl Acad Sci U S A 88:8656–8660

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Karasuyama H, Mukai K, Obata K, Tsujimura Y, Wada T (2011) Nonredundant roles of basophils in immunity. Annu Rev Immunol 29:45–69

    Article  CAS  PubMed  Google Scholar 

  5. Karasuyama H, Yamanishi Y (2014) Basophils have emerged as a key player in immunity. Curr Opin Immunol 31:1–7

    Article  CAS  PubMed  Google Scholar 

  6. Wada T, Ishiwata K, Koseki H, Ishikura T, Ugajin T, Ohnuma N, Obata K, Ishikawa R, Yoshikawa S, Mukai K et al (2010) Selective ablation of basophils in mice reveals their nonredundant role in acquired immunity against ticks. J Clin Invest 120:2867–2875

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Ohnmacht C, Schwartz C, Panzer M, Schiedewitz I, Naumann R, Voehringer D (2010) Basophils orchestrate chronic allergic dermatitis and protective immunity against helminths. Immunity 33:364–374

    Article  CAS  PubMed  Google Scholar 

  8. Sullivan BM, Liang HE, Bando JK, Wu D, Cheng LE, McKerrow JK, Allen CD, Locksley RM (2011) Genetic analysis of basophil function in vivo. Nat Immunol 12:527–535

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Sawaguchi M, Tanaka S, Nakatani Y, Harada Y, Mukai K, Matsunaga Y, Ishiwata K, Oboki K, Kambayashi T, Watanabe N et al (2012) Role of mast cells and basophils in IgE responses and in allergic airway hyperresponsiveness. J Immunol 188:1809–1818

    Article  CAS  PubMed  Google Scholar 

  10. Gibbs BF, Haas H, Falcone FH, Albrecht C, Vollrath IB, Noll T, Wolff HH, Amon U (1996) Purified human peripheral blood basophils release interleukin-13 and preformed interleukin-4 following immunological activation. Eur J Immunol 26:2493–2498

    Article  CAS  PubMed  Google Scholar 

  11. Gessner A, Mohrs K, Mohrs M (2005) Mast cells, basophils, and eosinophils acquire constitutive IL-4 and IL-13 transcripts during lineage differentiation that are sufficient for rapid cytokine production. J Immunol 174:1063–1072

    Article  CAS  PubMed  Google Scholar 

  12. Schroeder JT, MacGlashan DW Jr, Kagey-Sobotka A, White JM, Lichtenstein LM (1994) IgE-dependent IL-4 secretion by human basophils. The relationship between cytokine production and histamine release in mixed leukocyte cultures. J Immunol 153:1808–1817

    CAS  PubMed  Google Scholar 

  13. Schroeder JT (2011) Basophils: emerging roles in the pathogenesis of allergic disease. Immunol Rev 242:144–160

    Article  CAS  PubMed  Google Scholar 

  14. Sokol CL, Barton GM, Farr AG, Medzhitov R (2008) A mechanism for the initiation of allergen-induced T helper type 2 responses. Nat Immunol 9:310–318

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Siraganian RP, de Castro RO, Barbu EA, Zhang J (2010) Mast cell signaling: the role of protein tyrosine kinase Syk, its activation and screening methods for new pathway participants. FEBS Lett 584:4933–4940

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Law M, Morales JL, Mottram LF, Iyer A, Peterson BR, August A (2011) Structural requirements for the inhibition of calcium mobilization and mast cell activation by the pyrazole derivative BTP2. Int J Biochem Cell Biol 43:1228–1239

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Lantz CS, Boesiger J, Song CH, Mach N, Kobayashi T, Mulligan RC, Nawa Y, Dranoff G, Galli SJ (1998) Role for interleukin-3 in mast-cell and basophil development and in immunity to parasites. Nature 392:90–93

    Article  CAS  PubMed  Google Scholar 

  18. Le Gros G, Ben-Sasson SZ, Conrad DH, Clark-Lewis I, Finkelman FD, Plaut M, Paul WE (1990) IL-3 promotes production of IL-4 by splenic non-B, non-T cells in response to Fc receptor cross-linkage. J Immunol 145:2500–2506

    PubMed  Google Scholar 

  19. Kamijo S, Nunomura S, Ra C, Kanaguchi Y, Suzuki Y, Ogawa H, Okumura K, Takai T. (2015). Innate basophil IL-4 responses against allergens, endotoxin, and cytokines require the Fc receptor gamma-chain. J Allergy Clin Immunol 137:1613–1615.e2

  20. Hida S, Yamasaki S, Sakamoto Y, Takamoto M, Obata K, Takai T, Karasuyama H, Sugane K, Saito T, Taki S (2009) Fc receptor gamma-chain, a constitutive component of the IL-3 receptor, is required for IL-3-induced IL-4 production in basophils. Nat Immunol 10:214–222

    Article  CAS  PubMed  Google Scholar 

  21. Nakanishi K, Yoshimoto T, Tsutsui H, Okamura H (2001) Interleukin-18 regulates both Th1 and Th2 responses. Annu Rev Immunol 19:423–474

    Article  CAS  PubMed  Google Scholar 

  22. Yoshimoto T, Nakanishi K (2006) Roles of IL-18 in basophils and mast cells. Allergol Int 55:105–113

    Article  CAS  PubMed  Google Scholar 

  23. Liew FY, Pitman NI, McInnes IB (2010) Disease-associated functions of IL-33: the new kid in the IL-1 family. Nat Rev Immunol 10:103–110

    Article  CAS  PubMed  Google Scholar 

  24. Oboki K, Ohno T, Kajiwara N, Saito H, Nakae S (2010) IL-33 and IL-33 receptors in host defense and diseases. Allergol Int 59:143–160

    Article  CAS  PubMed  Google Scholar 

  25. Yoshimoto T, Tsutsui H, Tominaga K, Hoshino K, Okamura H, Akira S, Paul WE, Nakanishi K (1999) IL-18, although antiallergic when administered with IL-12, stimulates IL-4 and histamine release by basophils. Proc Natl Acad Sci U S A 96:13962–13966

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Kroeger KM, Sullivan BM, Locksley RM (2009) IL-18 and IL-33 elicit Th2 cytokines from basophils via a MyD88- and p38alpha-dependent pathway. J Leukoc Biol 86:769–778

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Siracusa MC, Saenz SA, Hill DA, Kim BS, Headley MB, Doering TA, Wherry EJ, Jessup HK, Siegel LA, Kambayashi T et al (2011) TSLP promotes interleukin-3-independent basophil haematopoiesis and type 2 inflammation. Nature 477:229–233

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Siracusa MC, Kim BS, Spergel JM, Artis D (2013) Basophils and allergic inflammation. J Allergy Clin Immunol 132:789–801, quiz 788

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Sabroe I, Jones EC, Usher LR, Whyte MK, Dower SK (2002) Toll-like receptor (TLR)2 and TLR4 in human peripheral blood granulocytes: a critical role for monocytes in leukocyte lipopolysaccharide responses. J Immunol 168:4701–4710

    Article  CAS  PubMed  Google Scholar 

  30. Bieneman AP, Chichester KL, Chen YH, Schroeder JT (2005) Toll-like receptor 2 ligands activate human basophils for both IgE-dependent and IgE-independent secretion. J Allergy Clin Immunol 115:295–301

    Article  CAS  PubMed  Google Scholar 

  31. Kamijo S, Takeda H, Tokura T, Suzuki M, Inui K, Hara M, Matsuda H, Matsuda A, Oboki K, Ohno T et al (2013) IL-33-mediated innate response and adaptive immune cells contribute to maximum responses of protease allergen-induced allergic airway inflammation. J Immunol 190:4489–4499

    CAS  PubMed  Google Scholar 

  32. Rosenstein RK, Bezbradica JS, Yu S, Medzhitov R (2014) Signaling pathways activated by a protease allergen in basophils. Proc Natl Acad Sci U S A 111:E4963–4971

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Zhu J, Yamane H, Paul WE (2010) Differentiation of effector CD4 T cell populations (*). Annu Rev Immunol 28:445–489

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Paul WE, Zhu J (2010) How are T(H)2-type immune responses initiated and amplified? Nature Reviews Immunology 10:225–235

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Mitre E, Nutman TB (2006) Basophils, basophilia and helminth infections. Chem Immunol Allergy 90:141–156

    CAS  PubMed  Google Scholar 

  36. Falcone FH, Zillikens D, Gibbs BF (2006) The 21st century renaissance of the basophil? Current insights into its role in allergic responses and innate immunity. Exp Dermatol 15:855–864

    Article  CAS  PubMed  Google Scholar 

  37. Mitre E, Taylor RT, Kubofcik J, Nutman TB (2004) Parasite antigen-driven basophils are a major source of IL-4 in human filarial infections. J Immunol 172:2439–2445

    Article  CAS  PubMed  Google Scholar 

  38. Hida S, Tadachi M, Saito T, Taki S (2005) Negative control of basophil expansion by IRF-2 critical for the regulation of Th1/Th2 balance. Blood 106:2011–2017

    Article  CAS  PubMed  Google Scholar 

  39. Oh K, Shen T, Le Gros G, Min B (2007) Induction of Th2 type immunity in a mouse system reveals a novel immunoregulatory role of basophils. Blood 109:2921–2927

    CAS  PubMed  Google Scholar 

  40. Charles N, Watford WT, Ramos HL, Hellman L, Oettgen HC, Gomez G, Ryan JJ, O’Shea JJ, Rivera J (2009) Lyn kinase controls basophil GATA-3 transcription factor expression and induction of Th2 cell differentiation. Immunity 30:533–543

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Sokol CL, Chu NQ, Yu S, Nish SA, Laufer TM, Medzhitov R (2009) Basophils function as antigen-presenting cells for an allergen-induced T helper type 2 response. Nat Immunol 10:713–720

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Yoshimoto T, Yasuda K, Tanaka H, Nakahira M, Imai Y, Fujimori Y, Nakanishi K (2009) Basophils contribute to T(H)2-IgE responses in vivo via IL-4 production and presentation of peptide-MHC class II complexes to CD4+ T cells. Nat Immunol 10:706–712

    Article  CAS  PubMed  Google Scholar 

  43. Perrigoue JG, Saenz SA, Siracusa MC, Allenspach EJ, Taylor BC, Giacomin PR, Nair MG, Du Y, Zaph C, van Rooijen N et al (2009) MHC class II-dependent basophil-CD4+ T cell interactions promote T(H)2 cytokine-dependent immunity. Nat Immunol 10:697–705

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Mellman I, Steinman RM (2001) Dendritic cells: specialized and regulated antigen processing machines. Cell 106:255–258

    Article  CAS  PubMed  Google Scholar 

  45. Kapsenberg ML (2003) Dendritic-cell control of pathogen-driven T-cell polarization. Nat Rev Immunol 3:984–993

    Article  CAS  PubMed  Google Scholar 

  46. Hammad H, Plantinga M, Deswarte K, Pouliot P, Willart MA, Kool M, Muskens F, Lambrecht BN (2010) Inflammatory dendritic cells—not basophils—are necessary and sufficient for induction of Th2 immunity to inhaled house dust mite allergen. J Exp Med 207:2097–2111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Kim S, Prout M, Ramshaw H, Lopez AF, LeGros G, Min B (2010) Cutting edge: basophils are transiently recruited into the draining lymph nodes during helminth infection via IL-3, but infection-induced Th2 immunity can develop without basophil lymph node recruitment or IL-3. J Immunol 184:1143–1147

    Article  CAS  PubMed  Google Scholar 

  48. Phythian-Adams AT, Cook PC, Lundie RJ, Jones LH, Smith KA, Barr TA, Hochweller K, Anderton SM, Hammerling GJ, Maizels RM et al (2010) CD11c depletion severely disrupts Th2 induction and development in vivo. J Exp Med 207:2089–2096

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Tawara I, Nieves E, Liu C, Evers R, Toubai T, Sun Y, Alrubaie M, Reddy P (2011) Host basophils are dispensable for induction of donor T helper 2 cell differentiation and severity of experimental graft-versus-host disease. Biol Blood Marrow Transplant 17:1747–1753

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Leyva-Castillo JM, Hener P, Michea P, Karasuyama H, Chan S, Soumelis V, Li M (2013) Skin thymic stromal lymphopoietin initiates Th2 responses through an orchestrated immune cascade. Nat Commun 4:2847

    Article  PubMed  Google Scholar 

  51. Suurmond J, Stoop JN, Rivellese F, Bakker AM, Huizinga TW, Toes RE (2014) Activation of human basophils by combined toll-like receptor- and FcεRI-triggering can promote Th2 skewing of naive T helper cells. Eur J Immunol 44:386–396

    Article  CAS  PubMed  Google Scholar 

  52. Zhong W, Su W, Zhang Y, Liu Q, Wu J, Di C, Zhang Z, Xia Z (2014) Basophils as a primary inducer of the T helper type 2 immunity in ovalbumin-induced allergic airway inflammation. Immunology 142:202–215

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Tang H, Cao W, Kasturi SP, Ravindran R, Nakaya HI, Kundu K, Murthy N, Kepler TB, Malissen B, Pulendran B (2010) The T helper type 2 response to cysteine proteases requires dendritic cell-basophil cooperation via ROS-mediated signaling. Nat Immunol 11:608–617

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Wakahara K, Van VQ, Baba N, Begin P, Rubio M, Delespesse G, Sarfati M (2013) Basophils are recruited to inflamed lungs and exacerbate memory Th2 responses in mice and humans. Allergy 68:180–189

    Article  CAS  PubMed  Google Scholar 

  55. Otsuka A, Nakajima S, Kubo M, Egawa G, Honda T, Kitoh A, Nomura T, Hanakawa S, Sagita Moniaga C, Kim B et al (2013) Basophils are required for the induction of Th2 immunity to haptens and peptide antigens. Nat Commun 4:1739

    Article  PubMed  Google Scholar 

  56. Gomez MR, Talke Y, Hofmann C, Ketelsen I, Hermann F, Reich B, Goebel N, Schmidbauer K, Dunger N, Bruhl H et al (2014) Basophils control T-cell responses and limit disease activity in experimental murine colitis. Mucosal Immunol 7:188–199

    Article  PubMed  Google Scholar 

  57. Kim S, Shen T, Min B (2009) Basophils can directly present or cross-present antigen to CD8 lymphocytes and alter CD8 T cell differentiation into IL-10-producing phenotypes. J Immunol 183:3033–3039

    Article  CAS  PubMed  Google Scholar 

  58. Khodoun MV, Orekhova T, Potter C, Morris S, Finkelman FD (2004) Basophils initiate IL-4 production during a memory T-dependent response. J Exp Med 200:857–870

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Denzel A, Maus UA, Rodriguez Gomez M, Moll C, Niedermeier M, Winter C, Maus R, Hollingshead S, Briles DE, Kunz-Schughart LA et al (2008) Basophils enhance immunological memory responses. Nat Immunol 9:733–742

    Article  CAS  PubMed  Google Scholar 

  60. Chen K, Xu W, Wilson M, He B, Miller NW, Bengten E, Edholm ES, Santini PA, Rath P, Chiu A et al (2009) Immunoglobulin D enhances immune surveillance by activating antimicrobial, proinflammatory and B cell-stimulating programs in basophils. Nat Immunol 10:889–898

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Charles N, Hardwick D, Daugas E, Illei GG, Rivera J (2010) Basophils and the T helper 2 environment can promote the development of lupus nephritis. Nat Med 16:701–707

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Walker JA, Barlow JL, McKenzie AN (2013) Innate lymphoid cells—how did we miss them? Nat Rev Immunol 13:75–87

    Article  CAS  PubMed  Google Scholar 

  63. Walker JA, McKenzie AN (2013) Development and function of group 2 innate lymphoid cells. Curr Opin Immunol 25:148–155

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. von Moltke J, Locksley RM (2014) I-L-C-2 it: type 2 immunity and group 2 innate lymphoid cells in homeostasis. Curr Opin Immunol 31:58–65

    Article  Google Scholar 

  65. Motomura Y, Morita H, Moro K, Nakae S, Artis D, Endo TA, Kuroki Y, Ohara O, Koyasu S, Kubo M (2014) Basophil-derived interleukin-4 controls the function of natural helper cells, a member of ILC2s, in lung inflammation. Immunity 40:758–771

    Article  CAS  PubMed  Google Scholar 

  66. Kim BS, Wang K, Siracusa MC, Saenz SA, Brestoff JR, Monticelli LA, Noti M, Tait Wojno ED, Fung TC, Kubo M et al (2014) Basophils promote innate lymphoid cell responses in inflamed skin. J Immunol 193:3717–3725

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Gordon S (2003) Alternative activation of macrophages. Nat Rev Immunol 3:23–35

    Article  CAS  PubMed  Google Scholar 

  68. Van Dyken SJ, Locksley RM (2013) Interleukin-4- and interleukin-13-mediated alternatively activated macrophages: roles in homeostasis and disease. Annu Rev Immunol 31:317–343

    Article  PubMed  PubMed Central  Google Scholar 

  69. Lumeng CN, Bodzin JL, Saltiel AR (2007) Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Invest 117:175–184

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Odegaard JI, Ricardo-Gonzalez RR, Goforth MH, Morel CR, Subramanian V, Mukundan L, Red Eagle A, Vats D, Brombacher F, Ferrante AW et al (2007) Macrophage-specific PPARgamma controls alternative activation and improves insulin resistance. Nature 447:1116–1120

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Wu D, Molofsky AB, Liang HE, Ricardo-Gonzalez RR, Jouihan HA, Bando JK, Chawla A, Locksley RM (2011) Eosinophils sustain adipose alternatively activated macrophages associated with glucose homeostasis. Science 332:243–247

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Lucas T, Waisman A, Ranjan R, Roes J, Krieg T, Muller W, Roers A, Eming SA (2010) Differential roles of macrophages in diverse phases of skin repair. J Immunol 184:3964–3977

    Article  CAS  PubMed  Google Scholar 

  73. Daley JM, Brancato SK, Thomay AA, Reichner JS, Albina JE (2010) The phenotype of murine wound macrophages. J Leukoc Biol 87:59–67

    Article  CAS  PubMed  Google Scholar 

  74. Egawa M, Mukai K, Yoshikawa S, Iki M, Mukaida N, Kawano Y, Minegishi Y, Karasuyama H (2013) Inflammatory monocytes recruited to allergic skin acquire an anti-inflammatory M2 phenotype via basophil-derived interleukin-4. Immunity 38:570–580

    Article  CAS  PubMed  Google Scholar 

  75. Obata-Ninomiya K, Ishiwata K, Tsutsui H, Nei Y, Yoshikawa S, Kawano Y, Minegishi Y, Ohta N, Watanabe N, Kanuka H et al (2013) The skin is an important bulwark of acquired immunity against intestinal helminths. J Exp Med 210:2583–2595

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Bleriot C, Dupuis T, Jouvion G, Eberl G, Disson O, Lecuit M (2015) Liver-resident macrophage necroptosis orchestrates type 1 microbicidal inflammation and type-2-mediated tissue repair during bacterial infection. Immunity 42:145–158

    Article  CAS  PubMed  Google Scholar 

  77. Anthony RM, Rutitzky LI, Urban JF Jr, Stadecker MJ, Gause WC (2007) Protective immune mechanisms in helminth infection. Nat Rev Immunol 7:975–987

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Mukai K, Matsuoka K, Taya C, Suzuki H, Yokozeki H, Nishioka K, Hirokawa K, Etori M, Yamashita M, Kubota T et al (2005) Basophils play a critical role in the development of IgE-mediated chronic allergic inflammation independently of T cells and mast cells. Immunity 23:191–202

    Article  CAS  PubMed  Google Scholar 

  79. Anthony RM, Kobayashi T, Wermeling F, Ravetch JV (2011) Intravenous gammaglobulin suppresses inflammation through a novel T(H)2 pathway. Nature 475:110–113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Campbell IK, Miescher S, Branch DR, Mott PJ, Lazarus AH, Han D, Maraskovsky E, Zuercher AW, Neschadim A, Leontyev D et al (2014) Therapeutic effect of IVIG on inflammatory arthritis in mice is dependent on the Fc portion and independent of sialylation or basophils. J Immunol 192:5031–5038

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Nakashima C, Otsuka A, Kitoh A, Honda T, Egawa G, Nakajima S, Nakamizo S, Arita M, Kubo M, Miyachi Y et al. (2014). Basophils regulate the recruitment of eosinophils in a murine model of irritant contact dermatitis. J Allergy Clin Immunol 134:100–107.e12

  82. Cheng LE, Sullivan BM, Retana LE, Allen CD, Liang HE, Locksley RM (2015) IgE-activated basophils regulate eosinophil tissue entry by modulating endothelial function. J Exp Med 212:513–524

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

This work is supported by research grants from the Japanese Ministry of Education, Culture, Sports, Science and Technology. The authors apologize for not citing all the relevant publications due to the space limitation.

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  1. Department of Immune Regulation, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, 113-8519, Japan

    Yoshinori Yamanishi & Hajime Karasuyama

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  1. Yoshinori Yamanishi
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Correspondence to Yoshinori Yamanishi.

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Yamanishi, Y., Karasuyama, H. Basophil-derived IL-4 plays versatile roles in immunity. Semin Immunopathol 38, 615–622 (2016). https://doi.org/10.1007/s00281-016-0568-y

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