The role of regulatory T cells in suppression and induction of inflammation

Many recent studies have focused on regulatory T cells (Tregs). These cells crucial to maintain immune tolerance and regulate the immune response to autoantigens, allergens, pathogens, and tumors. Epigenetic changes can provide a relatively stable pattern of Treg gene expression, producing suppressor cytokines such as interleukin-10 (IL-10), transforming growth factor beta (TGF-β), and IL-35, as well as inhibitory molecules, such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1), lymphocyte activation gene 3 (LAG-3), T-cell immunoreceptor with Ig and ITIM domains (TIGIT), cluster of differentiation 73 (CD73), and CD39. However, Tregs are a flexible and evolving cell population that depends on epigenetic factors and the microenvironment. Prolonged antigen stimulation during chronic infections causes T cell exhaustion, leading to the loss of effector function and decreased secretion of interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), and IL-2, as well as to the development of suppressor potential. Under certain conditions, the expression of the transcription factor Forkhead box P3 (Foxp3) decreases in Tregs, leading to the loss of suppressor activity and cell differentiation into memory T cells, which can maintain chronic inflammation. Infectious pathogens often stimulate Treg activity, which reduces the immune response and can potentially trigger autoimmune diseases. Tregs prevent inflammation and immune disorders by functioning in various non-lymphoid tissues. In addition, they can perform non-traditional functions in non-lymphoid organs associated with tissue development and homeostasis maintenance. Extracellular vesicles secreted by Tregs play an important role in both protective and pathogenic activities. These vesicles contain molecules that target recipient cells and regulate their function. Therefore, Tregs are involved in both the suppression and induction of acute and chronic immune inflammation. For this reason, current research need to be focused on developing new approaches to diagnose and treat autoimmune, infectious, and tumor diseases.