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- W4313373431 abstract "Abstract TIM-1+ B cells are enriched for IL-10+ B regulatory cells (Bregs). However, TIM-1+ B cells are also enriched for IL-4+ B effector 2 cells (Be2). Tolerogenic α-TIM-1 (RMT1-10) prolongs islet allograft survival (GS) by expanding (IL-10+) Bregs. Interestingly, IL-4KO and IL-4Rα-KO mice are deficient in Bregs and are not responsive to αTIM-1. To establish the importance of IL-4R signaling, and the source of IL-4 for Breg induction, we made tamoxifen (TAM) inducible BALB/c hCD20Cre.ERT2+/− X IL-4Rαfl/fl (B-IL-4RαKO) and hCD20Cre.ERT2+/− X IL-4/13fl/fl mice (B-IL-4KO) to respectively delete IL-4Rα or IL-4/IL-13 in B cells. After TAM, αTIM-1 treatment of alloimmunized B-IL-4RαKO mice had ↓ TIM-1+ B cells (50%), Be2 (50%) and Bregs (40%) vs. IL-4Rαfl/fl littermate controls and a concomittant 33%↑ in IFNγ+ and 33% ↓ in IL-10+ CD4 T cells, and a 20%↑ in IFNγ+ CD8 T cells vs. controls. Finally, α–TIM-1 led to >100d GS in 75% of control mice, but failed to improve GS in B-IL-4RαKO mice (MST 20d, p=0.03). Similarly, TAM treated B-IL-4KO mice had a 3x ↓ in Be2 and Bregs vs. IL-4fl/fl controls, and a 6x drop in IL-4+ CD4 T cells. Importantly, B-IL-4KO mice rejected islets more rapidly (MST 20d) than controls (MST 31d, p=0.04), and α–TIM-1 failed to improve B-IL-4KO GS (MST 17d) vs. controls (MST >100d). In contrast, in Th2 dominant OVA-induced allergic airway disease (AAD), B-IL-4KO mice had 3x decrease in total lymphocyte infiltrate, 5x decrease CD4 T cells and 8x decrease eosinophils in BAL fluid vs. controls. CD4+ T cells from whole lung tissue produced 2x less IL-4 and 3x less IL-5 vs. controls. Hence, IL-4 production by B cells is important for both Breg induction and Th2 polarization and absence of B cell IL-4/IL-13 promotes allograft rejection yet reduces AAD." @default.
- W4313373431 created "2023-01-06" @default.
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- W4313373431 date "2020-05-01" @default.
- W4313373431 modified "2023-09-27" @default.
- W4313373431 title "B Cell derived IL-4 promotes IL-10 secreting TIM-1+ regulatory B cell expansion and regulates Th2 T cell responses" @default.
- W4313373431 doi "https://doi.org/10.4049/jimmunol.204.supp.161.16" @default.
- W4313373431 hasPublicationYear "2020" @default.
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