Niche-specific control of tissue function by regulatory T cells-Current challenges and perspectives for targeting metabolic disease

Abstract

Tissue regulatory T cells (Tregs) exert pivotal functions in both immune and metabolic regulation, maintaining local tissue homeostasis, integrity, and function. Accordingly, Tregs play a crucial role in controlling obesity-induced inflammation and supporting efficient muscle function and repair. Depending on the tissue context, Tregs are characterized by unique transcriptomes, growth, and survival factors and T cell receptor (TCR) repertoires. This functional specialization offers the potential to selectively target context-specific Treg populations, tailoring therapeutic strategies to specific niches, thereby minimizing potential side effects. Here, we discuss challenges and perspectives for niche-specific Treg targeting, which holds promise for highly efficient and precise medical interventions to combat metabolic disease.

Keywords: ADCs; CAR Tregs; T2D; Treg engineering; antibody-drug conjugates; bispecific antibodies; bsAbs; immunometabolism; personalized medicines; therapeutic Treg targeting; tissue Treg; tissue Treg targeting in distinct niches; type 2 diabetes.