DNAM-1 regulates Foxp3 expression in regulatory T cells by interfering with TIGIT under inflammatory conditions

TLDR

Immune tolerance prevents autoimmunity, yet regulatory T cells lose suppressive function during inflammation. DNAM‑1 impairs Treg activity by outcompeting TIGIT for ligand binding, and its absence boosts TIGIT signaling to preserve Treg function during inflammation.

Abstract

Significance Immune tolerance is essential to prevent autoimmune responses, but it often needs to be limited for proper immune response. Regulatory T (Treg) cells play a crucial role in immune tolerance; however, their immune-suppressive function is restricted under inflammatory conditions. Here, we show that the activated immune receptor DNAM-1 limits Treg cell function regardless of DNAM-1–mediated intracellular signaling. We found that DNAM-1 competes with T cell immunoreceptor with Ig and ITIM domains (TIGIT) in binding to a common ligand. DNAM-1 deficiency enhances TIGIT signaling, thus resulting in the Treg cell function’s maintenance under inflammatory conditions. These results suggest that the DNAM-1 and TIGIT balance orchestrate Treg cell function for optimal immune reaction.