부산대학교 도서관

Foxp[3.sup.+]CD[4.sup.+] 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 PPAR[gamma] (peroxisome proliferator-activated receptor gamma) contains precursors of Tregs residing in visceral adipose tissue. This finding made sense given that PPAR[gamma], 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 PPAR[[gamma].sup.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. immunoregulation | single-cell RNA-seq | tissue Treg cell | precursor