Tissue Resident Foxp3+ Regulatory T Cells: Sentinels and Saboteurs in Health and Disease

Abstract

Foxp3+ regulatory T (Treg) cells are a CD4 T cell subset with unique immune regulatory function that are indispensable in immunity and tolerance. Their indisputable importance has been investigated in numerous disease settings and experimental models. Despite the extensive efforts in determining the cellular and molecular mechanisms operating their functions, our understanding their biology especially in vivo remains limited. There is emerging evidence that Treg cells resident in the non-lymphoid tissues play a central role in regulating tissue homeostasis, inflammation, and repair. Furthermore, tissue-specific properties of those Treg cells that allow them to express tissue specific functions have been explored. In this review, we will discuss the potential mechanisms and key cellular/molecular factors responsible for the homeostasis and functions of tissue resident Treg cells under steady-state and inflammatory conditions.

Editorial: Regulatory T cells in graft versus host disease

“…Recipient Tregs show increased persistence after conditioning regimens due to their increased radio-resistance when compared to Conventional T cells (Tcons). Such radio-resistance correlated with higher Bcl2 expression levels in rTregs and leads to the persistence of tissue resident recipient T cells, including Foxp3+ Tregs, after HSCT ( 7 ). Some studies have shown that after HSCT, recipient Tregs are able to expand in an IL2 dependent manner, providing some protection against GvHD.…”

The Role of LFA-1 for the Differentiation and Function of Regulatory T Cells—Lessons Learned from Different Transgenic Mouse Models

“…These ST2-positive tissues Treg express tissue-regenerative factors such as Amphiregulin (Areg) alongside T helper 2 (Th2)-associated factors, including high levels of transcription factor Gata3 [ 21 ]. Tissue homeostasis and specific functions of ST2-positive Treg cells have been characterized in different non-lymphoid tissues like visceral adipose tissue (VAT), muscle, colon, and skin [ 22 , 23 , 24 , 25 ]. All these Treg subtypes, including both FOXP3-dependent and -independent developed Treg populations, are thought to be essential for maintaining tissue homeostasis and immune tolerance [ 12 , 23 ].…”

The Dynamic Role of FOXP3+ Tregs and Their Potential Therapeutic Applications During SARS-CoV-2 Infection

“…FOXP3 + Tregs not only play essential role in the maintenance of immune homeostasis, but also play an indispensable role in regulating tissue homeostasis, inflammation and repair when resident in non-lymphoid tissues (51). The tissue resident Tregs own diverse functions, appeared in multiple sites including adipose tissue, cardiac muscle, skeletal muscle, lung, liver, central nervous system, skin and other tissues (51,52).…”

“…FOXP3 + Tregs not only play essential role in the maintenance of immune homeostasis, but also play an indispensable role in regulating tissue homeostasis, inflammation and repair when resident in non-lymphoid tissues (51). The tissue resident Tregs own diverse functions, appeared in multiple sites including adipose tissue, cardiac muscle, skeletal muscle, lung, liver, central nervous system, skin and other tissues (51,52). Recently we have revealed that insulin signaling induced the transition of visceral adipose tissue Tregs from CD73 hi ST2 lo subset into a CD73 lo ST2 hi subset through the HIF-1a/Med23-PPARg axis and thus influenced beige fat production (53).…”