| First Author | Hurdayal R | Year | 2017 |
| Journal | Proc Natl Acad Sci U S A | Volume | 114 |
| Issue | 40 | Pages | E8430-E8439 |
| PubMed ID | 28916732 | Mgi Jnum | J:268681 |
| Mgi Id | MGI:6095452 | Doi | 10.1073/pnas.1708125114 |
| Citation | Hurdayal R, et al. (2017) IL-4-producing B cells regulate T helper cell dichotomy in type 1- and type 2-controlled diseases. Proc Natl Acad Sci U S A 114(40):E8430-E8439 |
| abstractText | 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-4Ralpha) signaling on B cells in BALB/c mice (mb1(cre)IL-4Ralpha(-/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 (microMT) mice, we reveal a central role for B cell-derived IL-4 and IL-4Ralpha in the optimal induction of the susceptible type 2 phenotype to L. major infection. We further demonstrate that the absence of IL-4Ralpha 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-4Ralpha-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-4Ralpha-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. |
