The Study Of The Role Of NCoR1 In ST2~+ Regulatory T Cell Development And Adaptive Thermogenesis

Immune-metabolism crosstalk is very critical for the body to maintain energy equilibrium.As the prevalence of metabolism dysfunction,the immune mediators in adipose tissue have gathered strong attention.Previous studies characterized ST2~+Treg as a specialized fat-resident population.while its differentiation network and function mechanism on metabolism regulation remain largely unclear.Here,we report NCoR1represses ST2~+Treg differentiation globally.Mice lacking NCoR1 in Treg exhibit higher ratio of ST2~+subpopulation both in peripheral immune system and adipose tissue.These Treg are more sensitive to extracellular stimulus and secrete higher level of IL10 and several type II cytokines IL4,IL5 and IL13.Mechanically,NCoR1knockout Treg express higher level of ST2 and klrg1,with more opened chromatin accessibility in the regulation locus of these genes.Meanwhile,this subpopulation in peripheral immune system exhibits preferential upregulation of fat-Treg featured genes,which corresponds to the precursor of fat-Treg.At the Physiological level,mice with NCoR1 deficiency in Treg are more resistant to cold stimulation,concomitant with enhanced thermogenesis and energy expenditure,which finally results in slower age-associated body weight accumulation than that of wild type mice.These studies uncover a new role of NCoR1 in the differentiation program of ST2~+Treg and provide a new insight into Treg mediated metabolism regulation.