Tissue Tregs and Maintenance of Tissue Homeostasis

Regulatory T cells (Tregs) specifically expressing Forkhead box P3 (Foxp3) play roles in suppressing the immune response and maintaining immune homeostasis. After maturation in the thymus, Tregs leave the thymus and migrate to lymphoid tissues or non-lymphoid tissues. Increasing evidence indicates that Tregs with unique characteristics also have significant effects on non-lymphoid peripheral tissues. Tissue-resident Tregs, also called tissue Tregs, do not recirculate in the blood or lymphatics and attain a unique phenotype distinct from common Tregs in circulation. This review first summarizes the phenotype, function, and cytokine expression of these Tregs in visceral adipose tissue, skin, muscle, and other tissues. Then, how Tregs are generated, home, and are attracted to and remain resident in the tissue are discussed. Finally, how an increased understanding of these tissue Tregs might guide clinical treatment is discussed.