Basophils account for only 0.1–1% of all peripheral blood leukocytes. They were considered to be a redundant cell type for a long time. However, several findings show a non-redundant role for basophils in type 2 T-helper cell (Th2) immune responses in helminth infections, allergy and autoimmunity. Both immunoglobulin-E-dependent and -independent pathways have been described to contribute to basophil activation. In addition, several recent studies reported that basophils can function as antigen-presenting cells and are important in the initiation of Th2 immune responses. However, there are also conflicting studies that do not corroborate the importance of basophils in Th2 immune responses. This review discusses the role of basophils in Th2 immune responses in view of these recent findings.

1.
Ehrlich P: Beiträge zur Kenntnis der granulierten Zellen usw. Verh Physiol Ges Berlin 1879;21:53.
2.
Ishizaka T, DeBernardo R, Tomioka H, Lichtenstein LM, Ishizaka K: Identification of basophil granulocytes as a site of allergic histamine release. J Immunol 1972;108:1000–1008.
3.
Stone KD, Prussin C, Metcalfe DD: IgE, mast cells, basophils, and eosinophils. J Allergy Clin Immunol 2010;125:S73–S80.
4.
Karasuyama H: Nonredundant roles of basophils in immunity. Annu Rev Immunol 2011;29:45–69.
5.
Brunner T, Heusser C, Dahinden C: Human peripheral blood basophils primed by interleukin 3 (IL-3) produce IL-4 in response to immunoglobulin E receptor stimulation. J Exp Med 1993;177:605–611.
6.
Piccinni MP, Macchia D, Parronchi P, Giudizi MG, Bani D, Alterini R, Grossi A, Ricci M, Maggi E, Romagnani S: Human bone marrow non-B, non-T cells produce interleukin 4 in response to cross-linkage of Fcε and Fcγ receptors. Proc Natl Acad Sci UAS 1991;88:8656–8660.
7.
Schroeder JT, MacGlashan D, Kagey-Sobotka A, White JM, Lichtenstein LM: IgE-dependent IL-4 secretion by human basophils. The relationship between cytokine production and histamine release in mixed leukocyte cultures. J Immunol 1994;153:1808–1817.
8.
Schroeder JT, MacGlashan DW: Human basophils: mediator release and cytokine production. Adv Immunol 2001;77:93–122.
9.
Ohmori K, Luo Y, Jia Y, Nishida J, Wang Z, Bunting KD, Wang D, Huang H: IL-3 induces basophil expansion in vivo by directing granulocyte-monocyte progenitors to differentiate into basophil lineage-restricted progenitors in the bone marrow and by increasing the number of basophil/mast cell progenitors in the spleen. J Immunol 2009;182:2835–2841.
10.
Yoshimura-Uchiyama C, Yamaguchi M, Nagase H, Fujisawa T, Ra C, Matsushima K, Iwata T, Igarashi T, Yamamoto K, Hirai K: Comparative effects of basophil-directed growth factors. Biochem Biophys Res Commun 2003;302:201–206.
11.
Pecaric-Petkovic T, Didichenko SA, Kaempfer S, Spiegl N, Dahinden CA: Human basophils and eosinophils are the direct target leukocytes of the novel IL-1 family member IL-33. Blood 2009;113:1526–1534.
12.
Schroeder JT: Basophils: emerging roles in the pathogenesis of allergic disease. Immunol Rev 2011;242:144–160.
13.
Suzukawa M, Nagase H, Ogahara I, Han K, Tashimo H, Shibui A, Koketsu R, Nakae S, Yamaguchi M, Ohta K: Leptin enhances survival and induces migration, degranulation, and cytokine synthesis of human basophils. J Immunol 2011;186:5254–5260.
14.
Siracusa MC, Saenz SA, Hill DA, Kim BS, Headley MB, Doering TA, Wherry EJ, Jessup HK, Siegel LA, Kambayashi T: TSLP promotes interleukin-3-independent basophil haematopoiesis and type 2 inflammation. Nature 2011;477:229–233.
15.
Perrigoue JG, Saenz SA, Siracusa MC, Allenspach EJ, Taylor BC, Giacomin PR, Nair MG, Du Y, Zaph C, Van Rooijen N: MHC class II-dependent basophil-CD4+ T cell interactions promote TH2 cytokine-dependent immunity. Nat Immunol 2009;10:697–705.
16.
Comeau M, Ziegler S: The influence of TSLP on the allergic response. Mucosal Immunol 2009;3:138–147.
17.
He R, Geha R: Thymic stromal lymphopoietin. Ann NY Acad Sci 2010;1183:13–24.
18.
Liu YJ, Soumelis V, Watanabe N, Ito T, Wang YH, de Waal Malefyt R, Omori M, Zhou B, Ziegler SF: TSLP: an epithelial cell cytokine that regulates T cell differentiation by conditioning dendritic cell maturation. Immunology 2007;25:193–219.
19.
Soumelis V, Liu YJ: Human thymic stromal lymphopoietin: a novel epithelial cell-derived cytokine and a potential key player in the induction of allergic inflammation. Springer Semin Immunopathol 2004;25:325–333.
20.
Ziegler S, Artis D: Sensing the outside world: TSLP regulates barrier immunity. Nat Immunol 2010;11:289–293.
21.
Sloane DE, MacGlashan D: Basophils in anaphylaxis; in Castells MC (ed): Anaphylaxis and Hypersensitivity Reactions. New York, Springer, 2011, pp 69–87.
22.
Schneider E, Leite-de-Moraes M, Dy M: Histamine, immune cells and autoimmunity. Adv Exp Med Biol 2011;709:81–94.
23.
Tsujimura Y, Obata K, Mukai K, Shindou H, Yoshida M, Nishikado H, Kawano Y, Minegishi Y, Shimizu T, Karasuyama H: Basophils play a pivotal role in immunoglobulin-G-mediated but not immunoglobulin-E-mediated systemic anaphylaxis. Immunity 2008;28:581–589.
24.
Finkelman FD: IgE-dependent and independent effector mechanisms in human and murine anaphylaxis; in Castells MC (ed): Anaphylaxis and Hypersensitivity Reactions. New York, Springer, 2011, pp 127–144.
25.
Klos A, Tenner AJ, Johswich KO, Ager RR, Reis ES, Köhl J: The role of the anaphylatoxins in health and disease. Mol Immunol 2009;46:2753–2766.
26.
Guo RF, Ward PA: Role of C5a in inflammatory responses. Annu Rev Immunol 2005;23:821–852.
27.
Schneider E, Thieblemont N, De Moraes ML, Dy M: Basophils: new players in the cytokine network. Eur Cytokine Netw 2010;21:142–153.
28.
Gessner A, Mohrs K, Mohrs M: 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 2005;174:1063–1072.
29.
Ohnmacht C, Voehringer D: Basophil effector function and homeostasis during helminth infection. Blood 2009;113:2816–2825.
30.
Clarke EK, Xenakis JJ, Spencer LA: Differential expression of pre-formed cytokines in human basophils and eosinophils. J Allergy Clin Immunol 2011;127:AB208.
31.
Humphreys NE, Xu D, Hepworth MR, Liew FY, Grencis RK: IL-33, a potent inducer of adaptive immunity to intestinal nematodes. J Immunol 2008;180:2443–2449.
32.
Liew FY, Pitman NI, McInnes IB: Disease-associated functions of IL-33: the new kid in the IL-1 family. Nat Rev Immunol 2010;10:103–110.
33.
Lloyd CM: IL-33 family members and asthma-bridging innate and adaptive immune responses. Curr Opin Immunol 2010;22:800–806.
34.
Suzukawa M, Iikura M, Koketsu R, Nagase H, Tamura C, Komiya A, Nakae S, Matsushima K, Ohta K, Yamamoto K: An IL-1 cytokine member, IL-33, induces human basophil activation via its ST2 receptor. J Immunol 2008;181:5981–5989.
35.
Blom L, Poulsen BC, Jensen BM, Hansen A, Poulsen LK: IL-33 induces IL-9 production in human CD4+ T cells and basophils. PLoS One 2011;6:e21695.
36.
Sokol CL, Barton GM, Farr AG, Medzhitov R: A mechanism for the initiation of allergen-induced T helper type 2 responses. Nat Immunol 2008;9:310–318.
37.
Wang YH, Ito T, Homey B, Watanabe N, Martin R, Barnes CJ, McIntyre BW, Gilliet M, Kumar R: Maintenance and polarization of human TH2 central memory T cells by thymic stromal lymphopoietin-activated dendritic cells. Immunity 2006;24:827–838.
38.
Wang J, Xing F: Human TSLP-educated DCs. Cell Mol Immunol 2008;5:99–106.
39.
Wang Y, Liu Y: TSLP, OX40L, and IL-25 in allergic responses. Clin Exp Allergy J Br Soc Allergy Clin Immunol 2009;39:798–806.
40.
Wang YH, Angkasekwinai P, Lu N, Voo KS, Arima K, Hanabuchi S, Hippe A, Corrigan CJ, Dong C, Homey B: IL-25 augments type 2 immune responses by enhancing the expansion and functions of TSLP-DC-activated Th2 memory cells. J Exp Med 2007;204:1837–1847.
41.
Spiegl N, Didichenko S, McCaffery P, Langen H, Dahinden CA: Human basophils activated by mast cell-derived IL-3 express retinaldehyde dehydrogenase-II and produce the immunoregulatory mediator retinoic acid. Blood 2008;112:3762–3771.
42.
Boniface K, Blom B, Liu YJ, de Waal Malefyt R: From interleukin-23 to T-helper 17 cells: human T-helper cell differentiation revisited. Immunol Rev 2008;226:132–146.
43.
Klemann C, Je Raveney B, Oki S, Yamamura T: Retinoid signals and Th17-mediated pathology. Jpn J Clin Immunol 2009;32:20–28.
44.
Qi Y, Operario DJ, Oberholzer CM, Kobie JJ, Looney RJ, Georas SN, Mosmann TR: Human basophils express amphiregulin in response to T cell-derived IL-3. J Allergy Clin Immunol 2010;126:1260–1266.
45.
Zaiss DM, Yang L, Shah PR, Kobie JJ, Urban JF, Mosmann TR: Amphiregulin, a TH2 cytokine enhancing resistance to nematodes. Science 2006;314:1746.
46.
De Paulis A, Prevete N, Fiorentino I, Rossi FW, Staibano S, Montuori N, Ragno P, Longobardi A, Liccardo B, Genovese A: Expression and functions of the vascular endothelial growth factors and their receptors in human basophils. J Immunol 2006;177:7322–7331.
47.
Ahdieh M, Vandenbos T, Youakim A: Lung epithelial barrier function and wound healing are decreased by IL-4 and IL-13 and enhanced by IFN-γ. Am J Physiol Cell Physiol 2001;281:C2029–C2038.
48.
Ito Y, Satoh T, Takayama K, Miyagishi C, Walls A, Yokozeki H: Basophil recruitment and activation in inflammatory skin diseases. Allergy 2011;66:1107–1113.
49.
Naclerio RM, Proud D, Togias AG, Adkinson NF Jr, Meyers DA, Kagey-Sobotka A, Plaut M, Norman PS, Lichtenstein LM: Inflammatory mediators in late antigen-induced rhinitis. N Engl J Med 1985;313:65–70.
50.
Falcone FH, Haas H, Gibbs BF: The human basophil: a new appreciation of its role in immune responses. Blood 2000;96:4028–4038.
51.
Falcone F, Knol E, Gibbs B: The role of basophils in the pathogenesis of allergic disease. Clin Exp Allergy 2011;41:939–947.
52.
Knol EF, Gibbs BF: Editorial: basophil survival and immunomodulatory function are uniquely regulated by a novel MyD88-dependent pathway. J Leukoc Biol 2009;86:753–755.
53.
Kroeger KM, Sullivan BM, Locksley RM: IL-18 and IL-33 elicit Th2 cytokines from basophils via a MyD88- and p38α-dependent pathway. J Leukoc Biol 2009;86:769–778.
54.
van Panhuys N, Prout M, Forbes E, Min B, Paul WE, Le Gros G: Basophils are the major producers of IL-4 during primary helminth infection. J Immunol 2011;186:2719–2728.
55.
Voehringer D, Shinkai K, Locksley RM: Type 2 immunity reflects orchestrated recruitment of cells committed to IL-4 production. Immunity 2004;20:267–277.
56.
Chen K, Xu W, Wilson M, He B, Miller NW, Bengtén E, Edholm ES, Santini PA, Rath P, Chiu A: Immunoglobulin D enhances immune surveillance by activating antimicrobial, proinflammatory and B cell-stimulating programs in basophils. Nat Immunol 2009;10:889–898.
57.
Gomez MR, Talke Y, Goebel N, Hermann F, Reich B, Mack M: Basophils support the survival of plasma cells in mice. J Immunol 2010;185:7180–7185.
58.
Bosch X, Lozano F, Cervera R, Ramos-Casals M, Min B: Basophils, IgE, and autoantibody-mediated kidney disease. J Immunol 2011;186:6083–6090.
59.
Schuerwegh A, Ioan-Facsinay A, Dorjée A, Roos J, Bajema I, van der Voort E, Huizinga T, Toes R: Evidence for a functional role of IgE anticitrullinated protein antibodies in rheumatoid arthritis. Proc Natl Acad Sci USA 2010;107:2586–2591.
60.
Kaveri SV, Mouthon L, Bayry J: Basophils and nephritis in lupus. N Engl J Med 2010;363:1080–1082.
61.
Charles N, Hardwick D, Daugas E, Illei GG, Rivera J: Basophils and the T helper 2 environment can promote the development of lupus nephritis. Nat Med 2010;16:701–707.
62.
Nakanishi K: Basophils as APC in Th2 response in allergic inflammation and parasite infection. Curr Opin Immunol 2010;22:814–820.
63.
Smith D: IL-33: a tissue-derived cytokine pathway involved in allergic inflammation and asthma. Clin Exp Allergy 2010;40:200–208.
64.
Phillips C, Coward WR, Pritchard DI, Hewitt CRA: Basophils express a type 2 cytokine profile on exposure to proteases from helminths and house dust mites. J Leukoc Biol 2003;73:165–171.
65.
Banchereau J, Steinman RM: Dendritic cells and the control of immunity. Nature 1998;392:245–252.
66.
Sokol CL, Chu NQ, Yu S, Nish SA, Laufer TM, Medzhitov R: Basophils function as antigen-presenting cells for an allergen-induced T helper type 2 response. Nat Immunol 2009;10:713–720.
67.
Yoshimoto T, Yasuda K, Tanaka H, Nakahira M, Imai Y, Fujimori Y, Nakanishi K: Basophils contribute to TH2-IgE responses in vivo via IL-4 production and presentation of peptide-MHC class II complexes to CD4+ T cells. Nat Immunol 2009;10:706–712.
68.
Hammad H, Plantinga M, Deswarte K, Pouliot P, Willart MAM, Kool M, Muskens F, Lambrecht BN: Inflammatory dendritic cells – not basophils – are necessary and sufficient for induction of Th2 immunity to inhaled house dust mite allergen. J Exp Med 2010;207:2097–2111.
69.
Ohnmacht C, Voehringer D: Basophils protect against reinfection with hookworms independently of mast cells and memory Th2 cells. J Immunol 2010;184:344–350.
70.
Phythian-Adams AT, Cook PC, Lundie RJ, Jones LH, Smith KA, Barr TA, Hochweller K, Anderton SM, Hämmerling GJ, Maizels RM: CD11c depletion severely disrupts Th2 induction and development in vivo. J Exp Med 2010;207:2089–2096.
71.
Tang H, Cao W, Kasturi SP, Ravindran R, Nakaya HI, Kundu K, Murthy N, Kepler TB, Malissen B, Pulendran B: The T helper type 2 response to cysteine proteases requires dendritic cell-basophil cooperation via ROS-mediated signaling. Nat Immunol 2010;11:608–617.
72.
Ohnmacht C, Schwartz C, Panzer M, Schiedewitz I, Naumann R, Voehringer D: Basophils orchestrate chronic allergic dermatitis and protective immunity against helminths. Immunity 2010;33:364–374.
73.
Kim S, Prout M, Ramshaw H, Lopez AF, LeGros G, Min B: 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 2010;184:1143–1147.
74.
Sullivan BM, Liang HE, Bando JK, Wu D, Cheng LE, McKerrow JK, Allen CDC, Locksley RM: Genetic analysis of basophil function in vivo. Nat Immunol 2011;12:527–535.
75.
Crowle PK, Reed ND: Rejection of the intestinal parasite Nippostrongylus brasiliensis by mast cell-deficient W/Wv anemic mice. Infect Immun 1981;33:54–58.
76.
Voehringer D, Reese TA, Huang X, Shinkai K, Locksley RM: Type 2 immunity is controlled by IL-4/IL-13 expression in hematopoietic non-eosinophil cells of the innate immune system. J Exp Med 2006;203:1435–1446.
77.
Denzel A, Maus UA, Gomez MR, Moll C, Niedermeier M, Winter C, Maus R, Hollingshead S, Briles DE, Kunz-Schughart LA: Basophils enhance immunological memory responses. Nat Immunol 2008;9:733–742.
78.
Obata K, Mukai K, Tsujimura Y, Ishiwata K, Kawano Y, Minegishi Y, Watanabe N, Karasuyama H: Basophils are essential initiators of a novel type of chronic allergic inflammation. Blood 2007;110:913–920.
79.
Mukai K, Matsuoka K, Taya C, Suzuki H, Yokozeki H, Nishioka K, Hirokawa K, Etori M, Yamashita M, Kubota T: Basophils play a critical role in the development of IgE-mediated chronic allergic inflammation independently of T cells and mast cells. Immunity 2005;23:191–202.
80.
Mikhak Z, Luster AD: Chemokines in allergic responses: eosinophils, basophils, mast cells; in Neote K, Letts GL, Moser B (eds): Chemokine Biology – Basic Research and Clinical Application. Basel, Birkhäuser, 2007, vol 2, pp 27–41.
81.
Kepley CL, Cambier JC, Morel PA, Lujan D, Ortega E, Wilson BS, Oliver JM: Negative regulation of FcεRI signaling by FcγRII costimulation in human blood basophils. J Allergy Clin Immunol 2000;106:337–348.
82.
Meknache N, Jönsson F, Laurent J, Guinnepain MT, Daëron M: Human basophils express the glycosylphosphatidylinositol-anchored low-affinity IgG receptor FcγRIIIB (CD16B). J Immunol 2009;182:2542–2550.
83.
Malbec O, Daëron M: The mast cell IgG receptors and their roles in tissue inflammation. Immunol Rev 2007;217:206–221.
84.
Khodoun MV, Strait R, Armstrong L, Yanase N, Finkelman FD: Identification of markers that distinguish IgE- from IgG-mediated anaphylaxis. Proc Natl Acad Sci USA 2011;108:12413–12418.
85.
Vadas P, Gold M, Perelman B, Liss GM, Lack G, Blyth T, Simons FER, Simons KJ, Cass D, Yeung J: Platelet-activating factor, PAF acetylhydrolase, and severe anaphylaxis. N Engl J Med 2008;358:28–35.
86.
Kitzmüller C, Nagl B, Deifl S, Walterskirchen C, Jahn-Schmid B, Zlabinger G, Bohle B: Human blood basophils do not act as antigen-presenting cells for the major birch pollen allergen Bet v 1. Allergy 2012;67:593–600.
87.
Eckl-Dorna J, Ellinger A, Blatt K, Ghanim V, Steiner I, Pavelka M, Valent P, Valenta R, Niederberger V: Basophils are not the key antigen-presenting cells in allergic patients. Allergy 2012;67:601–608.
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