Tissue regulatory T cells

Abstract

Foxp3⁺ CD4⁺ regulatory T cells (Tregs) are an immune cell lineage endowed with immunosuppressive functionality in a wide array of contexts, including both anti-pathogenic and anti-self responses. In the past decades, our understanding of the functional diversity of circulating or lymphoid Tregs has grown exponentially. Only recently, the importance of Tregs residing within non-lymphoid tissues, such as visceral adipose tissue, muscle, skin and intestine, has been recognized. Not only are Tregs critical for influencing the kinetics and strength of immune responses, but the regulation of non-immune or parenchymal cells, also fall within the purview of tissue-resident or infiltrating Tregs. This review focuses on providing a systematic and comprehensive comparison of the molecular maintenance, local adaptation and functional specializations of Treg populations operating within different tissues.

Keywords: inflammation; regulatory T cells; tissue regulatory T cells; tissue repair.

Figure 1

Regulatory T cells (Tregs) residing within four major tissue sites. The majority of visceral adipose tissue Tregs, marked by their preferential expression of peroxisome proliferator‐activated receptor γ (PPARγ), are mainly thymically derived. Contrarily, intestinal Tregs are highly heterogeneous, in both preferential expression and origin. Some evidence has suggested skin Tregs are of thymic origin, and accumulate during neonatal life. Uniquely, the majority of muscle Tregs are derived from the circulation, but retain a preferential transcriptome relative to lymphoid Tregs. These four tissue Treg populations serve as important regulators of tissue inflammation and fibrosis, as well as playing a major role in facilitating tissue repair.