Pre-diagnostic genotyping identifies T1D subjects with impaired Treg IL-2 signaling and an elevated proportion of FOXP3⁺IL-17⁺ cells.

ABSTRACT: T-regulatory cells (Tregs) are essential for immune tolerance, and animal studies implicate their dysfunction in type 1 diabetes (T1D) pathogenesis. Tregs require interleukin-2 (IL-2) for their suppressive function, and variants in IL-2/IL-2R pathway genes have been associated with T1D. We previously reported that recent-onset T1D subjects have an increased population of FOXP3^lo Tregs that secrete the pro-inflammatory cytokine, interleukin-17 (IL-17). We hypothesize that IL-2 signaling defects may drive T1D development by skewing protective Tregs towards an inflammatory Th17 phenotype. Overall, we found that the proportion of FOXP3⁺IL-17⁺ cells in T1D subjects pre-diagnosis was unchanged compared with healthy controls. However, stratification by IL2RA singl

SUBMITTER: Marwaha AK 

PROVIDER: S-EPMC5843473 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature