Anti–IL-7 receptor-α reverses established type 1 diabetes in nonobese diabetic mice by modulating effector T-cell function
LF Lee, K Logronio, GH Tu, W Zhai… - Proceedings of the …, 2012 - National Acad Sciences
LF Lee, K Logronio, GH Tu, W Zhai, I Ni, L Mei, J Dilley, J Yu, A Rajpal, C Brown, C Appah…
Proceedings of the National Academy of Sciences, 2012•National Acad SciencesGenetic variation in the IL-7 receptor-α (IL-7R) gene is associated with susceptibility to
human type 1 diabetes (T1D). Here we investigate the therapeutic efficacy and mechanism
of IL-7Rα antibody in a mouse model of T1D. IL-7Rα antibody induces durable, complete
remission in newly onset diabetic mice after only two to three injections. IL-7 increases,
whereas IL-7Rα antibody therapy reduces, the IFN-γ–producing CD4+ (TH1) and IFN-γ–
producing CD8+ T cells. Conversely, IL-7 decreases and IL-7Rα antibody enhances the …
human type 1 diabetes (T1D). Here we investigate the therapeutic efficacy and mechanism
of IL-7Rα antibody in a mouse model of T1D. IL-7Rα antibody induces durable, complete
remission in newly onset diabetic mice after only two to three injections. IL-7 increases,
whereas IL-7Rα antibody therapy reduces, the IFN-γ–producing CD4+ (TH1) and IFN-γ–
producing CD8+ T cells. Conversely, IL-7 decreases and IL-7Rα antibody enhances the …
Genetic variation in the IL-7 receptor-α (IL-7R) gene is associated with susceptibility to human type 1 diabetes (T1D). Here we investigate the therapeutic efficacy and mechanism of IL-7Rα antibody in a mouse model of T1D. IL-7Rα antibody induces durable, complete remission in newly onset diabetic mice after only two to three injections. IL-7 increases, whereas IL-7Rα antibody therapy reduces, the IFN-γ–producing CD4+ (TH1) and IFN-γ–producing CD8+ T cells. Conversely, IL-7 decreases and IL-7Rα antibody enhances the inhibitory receptor Programmed Death 1 (PD-1) expression in the effector T cells. Programmed Death 1 blockade reversed the immune tolerance mediated by the IL-7Rα antibody therapy. Furthermore, IL-7Rα antibody therapy increases the frequency of regulatory T cells without affecting their suppressor activity. The durable efficacy and the multipronged tolerogenic mechanisms of IL-7Rα antibody therapy suggest a unique disease-modifying approach to T1D.
National Acad Sciences