The role of FOXP3+ regulatory T cells in human autoimmune and inflammatory diseases

Abstract

CD4 + regulatory T cells (T reg ) expressing the forkhead box protein 3 (FOXP3)transcription factor (T regs ) are instrumental for the prevention of autoimmune diseases. There is increasing evidence that the human T regulatory population is highly heterogeneous in phenotype and function. Numerous studies conducted in human autoimmune diseases have shown that T reg cells are impaired either in their suppressive function, in number, or both. However, the contribution of the FOXP3 + T reg subpopulations to the development of autoimmunity has not been delineated in detail. Rare genetic disorders that involve deficits in T reg function can be studied to develop a global idea of the impact of partial or complete deficiency in a specific molecular mechanism involved in T reg function. In patients with reduced T reg numbers (but no functional deficiency), the expansion of autologous T reg cells could be a suitable therapeutic approach: either infusion of invitro autologous expanded cells, infusion of interleukin (IL)-2/anti-IL-2 complex, or both. T reg biology-based therapies may not be suitable in patients with deficits of T reg function, unless their deficit can be corrected in vivo/in vitro.Finally, it is critical to consider the appropriate stage of autoimmune diseases at which administration of T reg cellular therapy can be most effective. We discuss conflicting data regarding whether T reg cells are more effectual at preventing the initiation of autoimmunity, ameliorating disease progression or curing autoimmunity itself.

Frequency of circulating subpopulations of T‐regulatory cells in patients with hidradenitis suppurativa

“…However, it should be noted that studies have shown phenotypical heterogeneity between tissue resident Tregs compared to Tregs in peripheral blood …”

“…However, it should be noted that studies have shown phenotypical heterogeneity between tissue resident Tregs compared to Tregs in peripheral blood. 29 In normal human skin, a considerable proportion of CD4+ T cells are formed by Tregs suggesting an important role of these cells in cutaneous homeostasis. 30 This homeostasis can be hampered by an altered bacterial biofilm on the skin, as demonstrated by the analysis of punch biopsies from clinically unaffected HS skin.…”

Regulatory T cells in solid organ transplantation

“…In this regard, the increased presence of regulatory T cells (Treg cells) within the peripheral circulation and graft microenvironment has been identified as being important in inducing graft tolerance . These cells are a part of the adaptive immune system and are considered to have key roles in immunosuppression and homeostasis in different disease settings …”

“…5,6 Regulatory T cells in the peripheral circulation are characterised as CD4 + with high levels of IL-2 receptor alpha chain (CD25 high ) and low levels of CD127 and intracellularly, expressing the forkhead box P3 transcription factor (FOXP3 + ). 5,6 However, the adoption of novel deeper immunophenotyping technologies has identified this phenotype to be more heterogeneous than initially considered. [6][7][8][9] (Figure 1) These data differ depending on the species, type of Treg cells, differentiation state and microenvironment.…”

Regulatory T cells: exploring mechanisms for future therapies

“…Future studies of the processes underlying development of T reg cells should focus on comprehensive analyses of the entire T cell receptor (TCR) repertoire, intra‐ and intercellular mechanisms that determine T reg cell generation and fate, and that pinpoint discriminating features between thymic and peripheral T reg cell development. The articles by Mohr et al and Attias et al will discuss the relative contribution of T reg cells in the control of autoimmune and chronic inflammatory diseases, and how developmental, homeostatic or functional defects contribute to disease onset.…”