DGKα and ζ deficiency causes regulatory T-cell dysregulation, destabilization, and conversion to pathogenic T-follicular helper cells to trigger IgG1-predominant autoimmunity.

DGKα and ζ deficiency in regulatory T cells causes their destabilization and conversion to pathogenic Tfh cells, triggering IgG1-predominant autoimmunity.

• Why it matters: Understanding how Tregs maintain immune tolerance is vital, as their dysfunction can lead to autoimmune diseases. The mechanisms that keep Tregs stable and suppress their conversion are not fully understood.
• What they did: Researchers used Treg-specific deletion of DGKα and ζ in mice to study their roles, analyzing signaling, metabolic, and transcriptional changes that lead to Treg destabilization and pathogenic conversion.
• The result: Loss of DGKs caused Tregs to become exTregs and Tfh-like cells, resulting in uncontrolled autoantibody production and multiorgan autoimmunity, highlighting DGKs as key regulators of immune self-tolerance.