High-fat diet and dyslipidemia synergistically contribute to T cell senescence in gut associated lymphoid tissue

Obesity can compromise immune response and immune surveillance. Recent studies have linked obesity with systemic T cell senescence and thymus involution. However, these studies failed to distinguish the influence of obesity from the influence of diet composition on premature T cell senescence. High-fat diet (HFD) can influence the immunity of gut-associated lymphoid tissue (GALT) preceding the onset of obesity. Despite GALT is sensitive to the changes in the dietary composition and metabolic status, it still remains elusive how HFD and obesity contribute to T cell senescence in the GALT. In this study, we illustrated the interplay of the HFD, obesity and intestinal immunity by comparing the immune features of diet-induced obese (DIO) to those of diet-resistant (DR) mice. As expected, DIO mice exhibited increased serum lipid levels and liver steatosis whereas dyslipidemia was absent in DR mice. DIO mice demonstrated a shift from naive to effector-memory (EM) phenotype in the T cells derived from the spleens and PPs. Moreover, DIO mice showed up-regulation of PD1 and KLRG1 on the T cells. Similar but mild trends were observed in the naive and EM T cells from DR mice. Furthermore, we proved that the senescent-like changes in splenic and PPs-derived T cells positively correlated with the serum lipid concentrations. Taken together, our results indicate that HFD components function synergistically with dyslipidemia to induce T cell senescence in the GALT.

Automated summary

Recent studies have linked obesity with systemic T cell senescence and thymus involution, but the influence of high-fat diet (HFD) and diet composition on premature T cell senescence remains unclear. This study showed that HFD components synergistically induce T cell senescence in the gut-associated lymphoid tissue (GALT) with dyslipidemia. The results demonstrated a shift from naive to effector-memory (EM) phenotype in T cells and up-regulation of PD1 and KLRG1 in DIO mice, highlighting the complex interplay of HFD, obesity, and intestinal immunity.