The CD137 Ligand Is Important for Type 1 Diabetes Development but Dispensable for the Homeostasis of Disease-Suppressive CD137⁺ FOXP3⁺ Regulatory CD4 T Cells.

ABSTRACT: CD137 modulates type 1 diabetes (T1D) progression in NOD mice. We previously showed that CD137 expression in CD4 T cells inhibits T1D, but its expression in CD8 T cells promotes disease development by intrinsically enhancing the accumulation of β-cell-autoreactive CD8 T cells. CD137 is expressed on a subset of FOXP3⁺ regulatory CD4 T cells (Tregs), and CD137⁺ Tregs are the main source of soluble CD137. Soluble CD137 suppresses T cells in vitro by binding to the CD137 ligand (CD137L) upregulated on activated T cells. To further study how the opposing functions of CD137 are regulated, we successfully targeted Tnfsf9 (encoding CD137L) in NOD mice using the CRISPR/Cas9 system (designated NOD.Tnfsf9 ^-/-). Relative to wild-type NOD mice, T1D develop

SUBMITTER: Foda BM 

PROVIDER: S-EPMC7296588 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature