| First Author | Lee LF | Year | 2012 |
| Journal | Proc Natl Acad Sci U S A | Volume | 109 |
| Issue | 31 | Pages | 12674-9 |
| PubMed ID | 22733769 | Mgi Jnum | J:188418 |
| Mgi Id | MGI:5440530 | Doi | 10.1073/pnas.1203795109 |
| Citation | Lee LF, et al. (2012) Anti-IL-7 receptor-alpha reverses established type 1 diabetes in nonobese diabetic mice by modulating effector T-cell function. Proc Natl Acad Sci U S A 109(31):12674-9 |
| abstractText | Genetic variation in the IL-7 receptor-alpha (IL-7R) gene is associated with susceptibility to human type 1 diabetes (T1D). Here we investigate the therapeutic efficacy and mechanism of IL-7Ralpha antibody in a mouse model of T1D. IL-7Ralpha antibody induces durable, complete remission in newly onset diabetic mice after only two to three injections. IL-7 increases, whereas IL-7Ralpha antibody therapy reduces, the IFN-gamma-producing CD4(+) (T(H)1) and IFN-gamma-producing CD8(+) T cells. Conversely, IL-7 decreases and IL-7Ralpha 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-7Ralpha antibody therapy. Furthermore, IL-7Ralpha antibody therapy increases the frequency of regulatory T cells without affecting their suppressor activity. The durable efficacy and the multipronged tolerogenic mechanisms of IL-7Ralpha antibody therapy suggest a unique disease-modifying approach to T1D. |
