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IL-4 Derived from Non-T Cells Induces Basophil- and IL-3-independent Th2 Immune Responses

  • Kim, Sohee (Department of Immunology, Lerner Research Institute, Cleveland Clinic Foundation) ;
  • Karasuyama, Hajime (Department of Immune Regulation and JST, CREST, Tokyo Medical and Dental University Graduate School) ;
  • Lopez, Angel F. (Division of Human Immunology, Center for Cancer Biology) ;
  • Ouyang, Wenjun (Genentech Inc.) ;
  • Li, Xiaoxia (Department of Immunology, Lerner Research Institute, Cleveland Clinic Foundation) ;
  • Gros, Graham Le (Malaghan Institute of Medical Research) ;
  • Min, Booki (Department of Immunology, Lerner Research Institute, Cleveland Clinic Foundation)
  • Received : 2013.11.20
  • Accepted : 2013.11.27
  • Published : 2013.12.31

Abstract

How Th2 immunity develops in vivo remains obscure. Basophils have been considered key innate cells producing IL-4, a cytokine essential for Th2 immunity. Increasing evidence suggests that basophils are dispensable for the initiation of Th2 immunity. In this study, we revisited the role of basophils in Th2 immune responses induced by various types of adjuvants. Mice deficient in IL-3 or IL-3 receptor, in which basophil lymph node recruitment is completely abolished, fully developed wild type level Th2 CD4 T cell responses in response to parasite antigen or papain immunization. Similar finding was also observed in mice where basophils are inducibly ablated. Interestingly, IL-4-derived from non-T cells appeared to be critical for the generation of IL-4-producing CD4 T cells. Other Th2 promoting factors including IL-25 and thymic stromal lymphopoietin (TSLP) were dispensable. Therefore, our results suggest that IL-3- and basophil-independent in vivo Th2 immunity develops with the help of non-T cell-derived IL-4, offering an additional mechanism by which Th2 type immune responses arise in vivo.

Keywords

References

  1. Karasuyama, H., K. Mukai, K. Obata, Y. Tsujimura, and T. Wada. 2011. Nonredundant roles of basophils in immunity. Annu. Rev. Immunol. 29: 45-69. https://doi.org/10.1146/annurev-immunol-031210-101257
  2. Min, B. 2008. Basophils: what they 'can do' versus what they 'actually do'. Nat. Immunol. 9: 1333-1339. https://doi.org/10.1038/ni.f.217
  3. Sokol, C. L. and R. Medzhitov. 2010. Role of basophils in the initiation of Th2 responses. Curr. Opin. Immunol. 22: 73-77. https://doi.org/10.1016/j.coi.2010.01.012
  4. Siracusa, M. C., J. G. Perrigoue, M. R. Comeau, and D. Artis. 2010. New paradigms in basophil development, regulation and function. Immunol. Cell. Biol. 88: 275-284. https://doi.org/10.1038/icb.2010.1
  5. Nakanishi, K. 2010. Basophils as APC in Th2 response in allergic inflammation and parasite infection. Curr. Opin. Immunol. 22: 814-820. https://doi.org/10.1016/j.coi.2010.10.018
  6. Sullivan, B. M., H. E. Liang, J. K. Bando, D. Wu, L. E. Cheng, J. K. McKerrow, C. D. Allen, and R. M. Locksley. 2011. Genetic analysis of basophil function in vivo. Nat. Immunol. 12: 527-535. https://doi.org/10.1038/ni.2036
  7. Hammad, H., M. Plantinga, K. Deswarte, P. Pouliot, M. A. Willart, M. Kool, F. Muskens, and B. N. Lambrecht. 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. https://doi.org/10.1084/jem.20101563
  8. Kim, S., M. Prout, H. Ramshaw, A. F. Lopez, G. LeGros, and B. Min. 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. https://doi.org/10.4049/jimmunol.0902447
  9. Phythian-Adams, A. T., P. C. Cook, R. J. Lundie, L. H. Jones, K. A. Smith, T. A. Barr, K. Hochweller, S. M. Anderton, G. J. Hammerling, R. M. Maizels, and A. S. MacDonald. 2010. CD11c depletion severely disrupts Th2 induction and development in vivo. J. Exp. Med. 207: 2089-2096. https://doi.org/10.1084/jem.20100734
  10. Koyasu, S. and K. Moro. 2011. Type 2 innate immune responses and the natural helper cell. Immunology 132: 475-481. https://doi.org/10.1111/j.1365-2567.2011.03413.x
  11. Barlow, J. L. and A. N. McKenzie. 2009. IL-25: a key requirement for the regulation of type-2 immunity. Biofactors 35: 178-182. https://doi.org/10.1002/biof.24
  12. Saenz, S. A., M. Noti, and D. Artis. 2010. Innate immune cell populations function as initiators and effectors in Th2 cytokine responses. Trends. Immunol. 31: 407-413. https://doi.org/10.1016/j.it.2010.09.001
  13. Saenz, S. A., M. C. Siracusa, J. G. Perrigoue, S. P. Spencer, J. F. Urban, Jr., J. E. Tocker, A. L. Budelsky, M. A. Kleinschek, R. A. Kastelein, T. Kambayashi, A. Bhandoola, and D. Artis. 2010. IL25 elicits a multipotent progenitor cell population that promotes T(H)2 cytokine responses. Nature 464: 1362-1366. https://doi.org/10.1038/nature08901
  14. Neill, D. R., S. H. Wong, A. Bellosi, R. J. Flynn, M. Daly, T. K. Langford, C. Bucks, C. M. Kane, P. G. Fallon, R. Pannell, H. E. Jolin, and A. N. McKenzie. 2010. Nuocytes represent a new innate effector leukocyte that mediates type-2 immunity. Nature 464: 1367-1370. https://doi.org/10.1038/nature08900
  15. Wang, Y. H., P. Angkasekwinai, N. Lu, K. S. Voo, K. Arima, S. Hanabuchi, A. Hippe, C. J. Corrigan, C. Dong, B. Homey, Z. Yao, S. Ying, D. P. Huston, and Y. J. Liu. 2007. IL-25 augments type 2 immune responses by enhancing the expansion and functions of TSLP-DC-activated Th2 memory cells. J. Exp. Med. 204: 1837-1847. https://doi.org/10.1084/jem.20070406
  16. Siracusa, M. C., S. A. Saenz, D. A. Hill, B. S. Kim, M. B. Headley, T. A. Doering, E. J. Wherry, H. K. Jessup, L. A. Siegel, T. Kambayashi, E. C. Dudek, M. Kubo, A. Cianferoni, J. M. Spergel, S. F. Ziegler, M. R. Comeau, and D. Artis. 2011. TSLP promotes interleukin-3-independent basophil haematopoiesis and type 2 inflammation. Nature 477: 229-233. https://doi.org/10.1038/nature10329
  17. Mukai K., K. Matsuoka, C. Taya, H. Suzuki, H. Yokozeki, K. Nishioka, K. Hirokawa, M. Etori, M. Yamashita, T. Kubota, Y. Minegishi, H. Yonekawa, and H. Karasuyama. 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. https://doi.org/10.1016/j.immuni.2005.06.011
  18. Wada, T., K. Ishiwata, H. Koseki, T. Ishikura, T. Ugajin, N. Ohnuma, K. Obata, R. Ishikawa, S. Yoshikawa, K. Mukai, Y. Kawano, Y. Minegishi, H. Yokozeki, N. Watanabe, and H. Karasuyama. 2010. Selective ablation of basophils in mice reveals their nonredundant role in acquired immunity against ticks. J. Clin. Invest. 120: 2867-2875. https://doi.org/10.1172/JCI42680
  19. Ohnmacht, C. and D. Voehringer. 2010. Basophils protect against reinfection with hookworms independently of mast cells and memory Th2 cells. J. Immunol. 184: 344-350. https://doi.org/10.4049/jimmunol.0901841
  20. Asquith, K. L., H. S. Ramshaw, P. M. Hansbro, K. W. Beagley, A. F. Lopez, and P. S. Foster. 2008. The IL-3/IL-5/ GM-CSF common receptor plays a pivotal role in the regulation of Th2 immunity and allergic airway inflammation. J. Immunol. 180: 1199-1206. https://doi.org/10.4049/jimmunol.180.2.1199
  21. Hu-Li, J., C. Pannetier, L. Guo, M. Lohning, H. Gu, C. Watson, M. Assenmacher, A. Radbruch, and W. E. Paul. 2001. Regulation of expression of IL-4 alleles: analysis using a chimeric GFP/IL-4 gene. Immunity 14: 1-11. https://doi.org/10.1016/S1074-7613(01)00084-X
  22. Lantz, C. S., J. Boesiger, C. H. Song, N. Mach, T. Kobayashi, R. C. Mulligan, Y. Nawa, G. Dranoff, and S. J. Galli. 1998. Role for interleukin-3 in mast-cell and basophil development and in immunity to parasites. Nature 392: 90-93. https://doi.org/10.1038/32190
  23. Sokol, C. L., G. M. Barton, A. G. Farr, and R. Medzhitov. 2008. A mechanism for the initiation of allergen-induced T helper type 2 responses. Nat. Immunol. 9: 310-318. https://doi.org/10.1038/ni1558
  24. van Panhuys, N., E. Forbes, N. van Panhuys, B. Min, and G. Le Gros. 2011. Basophils are the major producers of IL-4 during primary helminth infection. J. Immunol. 186: 2719-2728. https://doi.org/10.4049/jimmunol.1000940
  25. Noben-Trauth, N., J. Hu-Li, and W. E. Paul. 2000. Conventional, naive $CD4^+$ T cells provide an initial source of IL-4 during Th2 differentiation. J. Immunol. 165: 3620-3625. https://doi.org/10.4049/jimmunol.165.7.3620
  26. Tamachi, T., Y. Maezawa, K. Ikeda, S. Kagami, M. Hatano, Y. Seto, A. Suto, K. Suzuki, N. Watanabe, Y. Saito, T. Tokuhisa, I. Iwamoto, and H. Nakajima. 2006. IL-25 enhances allergic airway inflammation by amplifying a TH2 cell-dependent pathway in mice. J. Allergy Clin. Immunol. 118: 606-614. https://doi.org/10.1016/j.jaci.2006.04.051
  27. Perrigoue, J. G., S. A. Saenz, M. C. Siracusa, E. J. Allenspach, B. C. Taylor, P. R. Giacomin, M. G. Nair, Y. Du, C. Zaph, N. van Rooijen, M. R. Comeau, E. J. Pearce, T. M. Laufer, and D. Artis. 2009. MHC class II-dependent basophil-$CD4^+$ T cell interactions promote T(H)2 cytokine-dependent immunity. Nat. Immunol. 10: 697-705. https://doi.org/10.1038/ni.1740
  28. Yoshimoto, T., K. Yasuda, H. Tanaka, M. Nakahira, Y. Imai, Y. Fujimori, and K. Nakanishi. 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. https://doi.org/10.1038/ni.1737
  29. Fallon, P. G., S. J. Ballantyne, N. E. Mangan, J. L. Barlow, A. Dasvarma, D. R. Hewett, A. McIlgorm, H. E. Jolin, and A. N. McKenzie. 2006. Identification of an interleukin (IL)-25-dependent cell population that provides IL-4, IL-5, and IL-13 at the onset of helminth expulsion. J. Exp. Med. 203: 1105-1116. https://doi.org/10.1084/jem.20051615
  30. Wang, Y. H. and Y. J. Liu. 2009. Thymic stromal lymphopoietin, OX40-ligand, and interleukin-25 in allergic responses. Clin. Exp. Allergy 39: 798-806. https://doi.org/10.1111/j.1365-2222.2009.03241.x
  31. Smith, D. E. 2010. IL-33: a tissue derived cytokine pathway involved in allergic inflammation and asthma. Clin. Exp. Allergy 40: 200-208. https://doi.org/10.1111/j.1365-2222.2009.03384.x
  32. Townsend, M. J., P. G. Fallon, D. J. Matthews, H. E. Jolin, and A. N. McKenzie. 2000. T1/ST2-deficient mice demonstrate the importance of T1/ST2 in developing primary T helper cell type 2 responses. J. Exp. Med. 191: 1069-1076. https://doi.org/10.1084/jem.191.6.1069
  33. Maroof, A., M. Penny, R. Kingston, C. Murray, S. Islam, P. A. Bedford, and S. C. Knight. 2006. Interleukin-4 can induce interleukin-4 production in dendritic cells. Immunology 117: 271-279. https://doi.org/10.1111/j.1365-2567.2005.02305.x

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