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Publication : PPARγ marks splenic precursors of multiple nonlymphoid-tissue Treg compartments.

First Author  Li C Year  2021
Journal  Proc Natl Acad Sci U S A Volume  118
Issue  13 PubMed ID  33753509
Mgi Jnum  J:304009 Mgi Id  MGI:6681982
Doi  10.1073/pnas.2025197118 Citation  Li C, et al. (2021) PPARgamma marks splenic precursors of multiple nonlymphoid-tissue Treg compartments. Proc Natl Acad Sci U S A 118(13):e2025197118
abstractText  Foxp3(+)CD4(+) regulatory T cells (Tregs) regulate most types of immune response as well as several processes important for tissue homeostasis, for example, metabolism and repair. Dedicated Treg compartments-with distinct transcriptomes, T cell receptor repertoires, and growth/survival factor dependencies-have been identified in several nonlymphoid tissues. These Tregs are specifically adapted to function and operate in their home tissue-When, where, and how do they take on their specialized characteristics? We recently reported that a splenic Treg population expressing low levels of the transcription factor PPARgamma (peroxisome proliferator-activated receptor gamma) contains precursors of Tregs residing in visceral adipose tissue. This finding made sense given that PPARgamma, the "master regulator" of adipocyte differentiation, is required for the accumulation and function of Tregs in visceral adipose tissue but not in lymphoid tissues. Here we use single-cell RNA sequencing, single-cell Tcra and Tcrb sequencing, and adoptive-transfer experiments to show that, unexpectedly, the splenic PPARgamma(lo) Treg population is transcriptionally heterogeneous and engenders Tregs in multiple nonlymphoid tissues beyond visceral adipose tissue, such as skin and liver. The existence of a general pool of splenic precursors for nonlymphoid-tissue Tregs opens possibilities for regulating their emergence experimentally or therapeutically.
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