Description

Molecular Mechanism underlying Human Treg Cell Heterogenicity

Gang Yi^1#, Yi Zhao^2#, Rui Liang¹, Dan Li^1,3, Xun Xu², Xiao Liu²* & Bin Li^1,3*

¹Shanghai Institute of Immunology & Department of Immunology and Microbiology, Shanghai JiaoTong University School of Medicine, Shanghai 200025; ²China National Genebank-Shenzhen, BGI-Shenzhen, Shenzhen, 518083 China; ³CAS Center for Excellence in Molecular Cell Science, Unit of Molecular Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, China

*Corresponding authors

CD4⁺CD25⁺FOXP3⁺ regulatory T cells (Tregs) is essential and critical for maintaining host immune homeostasis. Inflammatory cytokines such as IL-1β and IL-6 have been implicated as factors inducing the conversion of FOXP3⁺Tregs to either IFNg⁺Th1-like or IL-17⁺Th17-like cells, but the underlying mechanism remain unclear. Here we report that there is considerable heterogeneity within human CD4⁺CD25⁺CD127^- Treg subsets. Our single cell RNA-seq data show that different Treg subsets respond to environmental cues are different. We defined several subsets of signature genes including GATA3 and LGALS9 which suggested the differential response of FOXP3+Treg subsets under inflammation. Our data may provide new molecular bases for the functional instability of human Tregs under inflammation.