Phenotype and function of tissue-resident unconventional Foxp3-expressing CD4+ regulatory T cells

•Regulatory T cells (Tregs) are identified as a part of non-inflammatory process.•Tissue-resident Tregs have found in adipose, skin, muscle, intestine, central nervous system.•Tissue-specific Tregs have unique TCR repertoires, tissue specific factors, activation markers.•Tissue-resident Tregs possess distinguished function profiles in specific tissues.

It is becoming increasingly clear that regulatory T cells (Treg cells) in specific tissues are important parts of immune system. Tissue-resident Treg cells, which are largely Foxp3-expressing CD4+ Treg cells, are distinct from one another and conventional Treg cells, and have tissue-specific phenotype and function. They have roles in improving insulin sensitivity in adipose tissue, promoting muscle repair, limiting inflammation in intestine, skin and central nervous system. In this Review, we discuss the current understanding of phenotype and function of tissue-resident Treg cells. Understanding phenotypic and functional diversity in different tissues could provide new insight into Treg cells development and investigation.