T-bet+ CXCR3+ VAT Tregs limit antiviral response in adipose tissue and suppress virally-induced insulin resistance 3224

Abstract Description Viral infections, such as those caused by lymphocytic choriomeningitis virus (LCMV), can trigger a T-cell-mediated inflammatory response in visceral adipose tissue (VAT), leading to metabolic dysfunctions such as insulin resistance. VAT contains a heterogeneous population of regulatory T cells (Tregs), including distinct subsets that express either ST2 or CXCR3, which restrain obesity-induced inflammation and maintain VAT homeostasis. However, the effect of viral infections on these VAT Treg subsets and their respective functions during viral infections remain unclear. In this study, we found that acute LCMV Armstrong infection promoted the accumulation of T-bet+ CXCR3+ VAT Tregs while disproportionally suppressing the ST2+ VAT Treg subset. Treg-specific ablation of T-bet in Tbx21f/f Foxp3cre mice led to a marked loss of CXCR3+ Tregs alongside an increase in ST2+Tregs. Notably, disruption of the T-bet+ CXCR3+ Treg subset significantly increased the accumulation of LCMV-specific CD8+ and CD4+ T cells and promoted their production of inflammatory cytokines, particularly IFNg, in the VAT, but not spleen of LCMV-infected mice. Consequently, Tbx21f/f Foxp3cre mice showed worsened insulin resistance by day 15 post-LCMV Armstrong infection, possibly due to increased IFNg. These findings suggest that T-bet+ CXCR3+ Tregs are critical in limiting LCMV-induced VAT inflammation and mitigating virally-induced insulin resistance, a function that cannot be compensated by ST2+ VAT Tregs. Topic Categories Viral Immunology (VIR)