PhD Candidate University of California, Irvine, United States
Introduction/Rationale: Type 2 Diabetes (T2D) is characterized by adipose inflammation dominated by Th17 cells. Standard mouse models poorly recapitulate human T2D. We discovered CD1a, a lipid antigen-presenting molecule absent in mice, mediates protective T cell responses in T2D mouse models. We hypothesized that CD1a lipid antigen presentation drives inflammation in response to High Fat Diets (HFD). We generated transgenic mice expressing human CD1a (hCD1a) and fed them HFD 45% fat for up to 34 weeks. Adipose tissue immune infiltrates were characterized by flow cytometry.
Methods: We generated transgenic mice expressing human CD1a (hCD1a) and fed them HFD 45% fat for up to 34 weeks. Adipose tissue immune infiltrates were characterized by flow cytometry.
Results: hCD1a HFD had a significant increase of infiltrating CD8+ and CD4+ T Cells into adipose compared to WT after 34 weeks on diet. hCD1a HFD infiltrates were predominantly TCRβ+ and antigen-experienced when compared to WT HFD or hCD1a Low Fat diet (LFD) mice. hCD1a HFD mice had lower fasting insulin levels and HOMA-IR as early as week 6 on diet.They also had lower gonadal fat pad weight despite overall weight remaining comparable to WT HFD.
Conclusion: We demonstrate that CD1a mediates robust T cell infiltration into adipose tissue under HFD concurrent with protection from insulin resistance, suggesting a protective role for CD1a-mediated T cell inflammation. These data may explain limitations of traditional mouse models. This work identifies CD1a-lipid interactions as novel therapeutic targets and suggests immunomodulation strategies that enhance rather than suppress specific T cell responses in metabolic disease.
