We thank Glenn Dranoff for the permission to use the IL-3 deficient mice. We thank Maria Hutterer for help in histology, Rüdiger Eder and Jasmin Stahl for support in FACS-sorting and Klaus Stark for help with real time PCR. This work was supported by grants from the Deutsche Forschungsgemeinschaft (M.M.)
1 Wedemeyer, J. & Galli, S.J. Mast cells and basophils in acquired immunity. Br. Med. Bull. 56, 936-955 (2000).
2 Khodoun, M.V., Orekhova, T., Potter, C., Morris, S., & Finkelman, F.D. Basophils initiate IL-4 production during a memory T-dependent response. J. Exp. Med. 200, 857-870 (2004).
3 Oh, K., Shen, T., Le, G.G., & Min, B. Induction of Th2 type immunity in a mouse system reveals a novel immunoregulatory role of basophils. Blood 109, 2921-2927 (2007).
4 Sokol, C.L., Barton, G.M., Farr, A.G., & Medzhitov, R. A mechanism for the initiation of allergen-induced T helper type 2 responses. Nat. Immunol. 9, 310-318 (2008).
5 Min, B. et al. Basophils produce IL-4 and accumulate in tissues after infection with a Th2- inducing parasite. J. Exp. Med. 200, 507-517 (2004).
6 Zheng, W. & Flavell, R.A. The transcription factor GATA-3 is necessary and sufficient for Th2 cytokine gene expression in CD4 T cells. Cell 89, 587-596 (1997).
7 Diehl, S. et al. Induction of NFATc2 expression by interleukin 6 promotes T helper type 2 differentiation. J. Exp. Med. 196, 39-49 (2002).
8 Hammad, H. et al. 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 (2010).
9 Ohnmacht, C., Schwartz, C., Panzer, M., Schiedewitz, I., Naumann, R., & Voehringer, D. Basophils orchestrate chronic allergic dermatitis and protective immunity against helminths. Immunity. 33, 364-374 (2010).
10 Sullivan, B.M. et al. Genetic analysis of basophil function in vivo. Nat. Immunol. 12, 527-535 (2011).
11 Tang, H. et al. The T helper type 2 response to cysteine proteases requires dendritic cell basophil cooperation via ROS-mediated signaling. Nat. Immunol. 11, 608-617 (2010).
12 Lantz, C.S. et al. Role for interleukin-3 in mast-cell and basophil development and in immunity to parasites. Nature 392, 90-93 (1998).
13 Denzel, A. et al. Basophils enhance immunological memory responses. Nat. Immunol. 9, 733-742 (2008).
14 Mack, M. et al. Identification of antigen-capturing cells as basophils. J. Immunol. 174, 735-741 (2005).
15 Valent, P., Besemer, J., Muhm, M., Majdic, O., Lechner, K., & Bettelheim, P. Interleukin 3 activates human blood basophils via high-affinity binding sites. Proc. Natl. Acad. Sci. U. S. A 86, 5542-5546 (1989).
16 Ohnmacht, C. & Voehringer, D. Basophil effector function and homeostasis during helminth infection. Blood 113, 2816-2825 (2009).
17 Kim, S., Prout, M., Ramshaw, H., Lopez, A.F., 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. 184, 1143-1147 (2010).
18 Shen, T. et al. T cell-derived IL-3 plays key role in parasite infection-induced basophil production but is dispensable for in vivo basophil survival. Int. Immunol. 20, 1201-1209 (2008).
19 Schroeder, J.T., Chichester, K.L., & Bieneman, A.P. Human basophils secrete IL-3: evidence of autocrine priming for phenotypic and functional responses in allergic disease. J. Immunol. 182, 2432-2438 (2009).
20 Bruhl, H. et al. Important role of interleukin-3 in the early phase of collagen-induced arthritis. Arthritis Rheum. 60, 1352-1361 (2009).
21 Didichenko, S.A., Spiegl, N., Brunner, T., & Dahinden, C.A. IL-3 induces a Pim1-dependent antiapoptotic pathway in primary human basophils. Blood 112, 3949-3958 (2008).
22 Baumgart, D.C. & Carding, S.R. Inflammatory bowel disease: cause and immunobiology. Lancet 369, 1627-1640 (2007).
23 Baumgart, D.C. & Sandborn, W.J. Inflammatory bowel disease: clinical aspects and established and evolving therapies. Lancet 369, 1641-1657 (2007).
24 Morrissey, P.J., Charrier, K., Braddy, S., Liggitt, D., & Watson, J.D. CD4+ T cells that express high levels of CD45RB induce wasting disease when transferred into congenic severe combined immunodeficient mice. Disease development is prevented by cotransfer of purified CD4+ T cells. J. Exp. Med. 178, 237-244 (1993).
25 Ito, H. & Fathman, C.G. CD45RBhigh CD4+ T cells from IFN-gamma knockout mice do not induce wasting disease. J. Autoimmun. 10, 455-459 (1997).
26 Totsuka, T. et al. Therapeutic effect of anti-OX40L and anti-TNF-alpha MAbs in a murine model of chronic colitis. Am. J. Physiol Gastrointest. Liver Physiol 284, G595-G603 (2003).
27 Powrie, F., Leach, M.W., Mauze, S., Menon, S., Caddle, L.B., & Coffman, R.L. Inhibition of Th1 responses prevents inflammatory bowel disease in scid mice reconstituted with CD45RBhi CD4+ T cells. Immunity. 1, 553-562 (1994).
28 Becker, C. et al. Cutting edge: IL-23 cross-regulates IL-12 production in T cell-dependent experimental colitis. J. Immunol. 177, 2760-2764 (2006).
29 Izcue, A. et al. Interleukin-23 restrains regulatory T cell activity to drive T cell-dependent colitis. Immunity. 28, 559-570 (2008).
30 Wirtz, S. et al. Cutting edge: chronic intestinal inflammation in STAT-4 transgenic mice: characterization of disease and adoptive transfer by TNF- plus IFN-gamma-producing CD4+ T cells that respond to bacterial antigens. J. Immunol. 162, 1884-1888 (1999).
31 Berg, D.J. et al. Enterocolitis and colon cancer in interleukin-10-deficient mice are associated with aberrant cytokine production and CD4(+) TH1-like responses. J. Clin. Invest 98, 1010-1020 (1996).
32 Kuhn, R., Lohler, J., Rennick, D., Rajewsky, K., & Muller, W. Interleukin-10-deficient mice develop chronic enterocolitis. Cell 75, 263-274 (1993).
33 Siracusa, M.C. et al. TSLP promotes interleukin-3-independent basophil haematopoiesis and type 2 inflammation. Nature 477, 229-233 (2011).
34 Wada, T. et al. Selective ablation of basophils in mice reveals their nonredundant role in acquired immunity against ticks. J. Clin. Invest 120, 2867-2875 (2010).
35 Hill, D.A. et al. Commensal bacteria-derived signals regulate basophil hematopoiesis and allergic inflammation. Nat. Med. 18, 538-546 (2012).
36 Yoshimoto, T. et al. 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 (2009).
37 Chen, K. et al. Immunoglobulin D enhances immune surveillance by activating antimicrobial, proinflammatory and B cell-stimulating programs in basophils. Nat.Immunol. 10, 889-898 (2009).
38 Rodriguez Gomez M., Talke, Y., Goebel, N., Hermann, F., Reich, B., & Mack, M. Basophils support the survival of plasma cells in mice. J. Immunol. 185, 7180-7185 (2010).
39 Charles, N., Hardwick, D., Daugas, E., Illei, G.G., & Rivera, J. Basophils and the T helper 2 environment can promote the development of lupus nephritis. Nat. Med. 16, 701-707 (2010).
40 Obata, K. et al. Basophils are essential initiators of a novel type of chronic allergic inflammation. Blood 110, 913-920 (2007).
41 Ansel, K.M., Lee, D.U., & Rao, A. An epigenetic view of helper T cell differentiation. Nat. Immunol. 4, 616-623 (2003).
42 Anthony, R.M., Kobayashi, T., Wermeling, F., & Ravetch, J.V. Intravenous gammaglobulin suppresses inflammation through a novel T(H)2 pathway. Nature 475, 110-113 (2011).
43 Niess, J.H., Leithauser, F., Adler, G., & Reimann, J. Commensal gut flora drives the expansion of proinflammatory CD4 T cells in the colonic lamina propria under normal and inflammatory conditions. J. Immunol. 180, 559-568 (2008).
44 Weinstock, J.V. & Elliott, D.E. Helminths and the IBD hygiene hypothesis. Inflamm. Bowel. Dis. 15, 128-133 (2009).
45 Summers, R.W., Elliott, D.E., Urban, J.F., Jr., Thompson, R., & Weinstock, J.V. Trichuris suis therapy in Crohn's disease. Gut 54, 87-90 (2005).
46 Summers, R.W., Elliott, D.E., Urban, J.F., Jr., Thompson, R.A., & Weinstock, J.V. Trichuris suis therapy for active ulcerative colitis: a randomized controlled trial. Gastroenterology 128, 825-832 (2005).
47 Finkelman, F.D. & Morris, S.C. Development of an assay to measure in vivo cytokine production in the mouse. Int. Immunol. 11, 1811-1818 (1999).
48 Obermeier, F. et al. In vivo CpG DNA/toll-like receptor 9 interaction induces regulatory properties in CD4+CD62L+ T cells which prevent intestinal inflammation in the SCID transfer model of colitis. Gut 54, 1428-1436 (2005).