An IL-2 mutein increases regulatory T cell suppression of dendritic cells via IL-10 and CTLA-4 to promote T cell anergy.

ABSTRACT: Interleukin-2 (IL-2) variants with increased CD25 dependence that selectively expand Foxp3⁺ regulatory T (T_R) cells are in clinical trials for treating inflammatory diseases. Using an Fc-fused IL-2 mutein (Fc.IL-2 mutein) we developed that prevents diabetes in non-obese diabetic (NOD) mice, we show that Fc.IL-2 mutein induced an activated T_R population with elevated proliferation, a transcriptional program associated with Stat5- and T cell receptor-dependent gene modules, and high IL-10 and CTLA-4 expression. Increased IL-10 signaling limited surface major histocompatibility complex class II upregulation during conventional dendritic cell (cDC) maturation, while increased CTLA-4-dependent transendocytosis led to the transfer of CD80 and CD86 co-stimulatory

SUBMITTER: Jamison BL 

PROVIDER: S-EPMC11602548 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature