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标题：IL-4–producing B cells regulate T helper cell dichotomy in type 1- and type 2-controlled diseases
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作者：Ramona Hurdayal ; Hlumani H. Ndlovu ; Mélanie Revaz-Breton 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2017
卷号：114
期号：40
页码：E8430-E8439
DOI：10.1073/pnas.1708125114
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Interleukin-4 (IL-4)–induced T helper (Th) 2 cells promote susceptibility to the protozoan parasite Leishmania major , while conferring immunity to the intestinal trematode Schistosoma mansoni . Here, we report that abrogation of IL-4 receptor alpha (IL-4Rα) signaling on B cells in BALB/c mice ( mb1 ^creIL-4Rα^–/lox) transformed nonhealer BALB/c to a healer phenotype with an early type 1 and dramatically reduced type 2 immune response and an absence of ulceration and necrosis during cutaneous leishmaniasis. From adoptive reconstitution and mixed bone-marrow chimera studies in B cell-deficient (µMT) mice, we reveal a central role for B cell-derived IL-4 and IL-4Rα in the optimal induction of the susceptible type 2 phenotype to L. major infection. We further demonstrate that the absence of IL-4Rα signaling on B cells exacerbated S. mansoni -induced mortality and pathology in BALB/c mice, due to a diminished type 2 immune response. In both disease models, IL-4Rα–responsive B cells displayed increased IL-4 production as early as day 1 after infection. Together, these results demonstrate that IL-4–producing and IL-4Rα–responsive B cells are critical in regulating and assisting early T helper dichotomy toward Th2 responses, which are detrimental in cutaneous leishmaniasis but beneficial in acute schistosomiasis.
关键词：IL-4R alpha ; B cells ; leishmaniasis ; schistosomiasis ; mouse