Intestinal regulatory T cell (Intestinal Treg)

Intestinal regulatory T cells (Tregs) are a specialized subset of CD4+ T lymphocytes defined by the expression of the transcription factor FOXP3, which serve as the primary mediators of immune tolerance in the gastrointestinal tract (PMID: 24232444). They are essential for maintaining homeostasis by suppressing inflammatory responses against harmless dietary proteins and the commensal microbiota through the production of anti-inflammatory cytokines like IL-10 and TGF-beta (PMID: 17202235). In the gut, these cells exist as a heterogeneous population, including thymus-derived Tregs and peripherally induced Tregs, the latter of which are often induced by microbial metabolites such as short-chain fatty acids (PMID: 24336202). Dysregulation or a reduction in intestinal Treg frequency is a hallmark of inflammatory bowel diseases (IBD), such as Crohn's disease and ulcerative colitis, where the loss of tolerance leads to chronic mucosal damage (PMID: 30635652). Conversely, in the context of colorectal cancer, an accumulation of Tregs can inhibit effective anti-tumor immune surveillance, facilitating disease progression. Therapeutic approaches targeting these cells include the use of low-dose IL-2 to selectively expand Treg populations, the administration of specific probiotics to induce their differentiation, and the development of engineered adoptive cell therapies designed to restore intestinal immune balance (PMID: 31034749).

Other names

Gut-resident regulatory T cellColonic regulatory T cellFOXP3+ intestinal T cellRORgamma-t+ TregMucosal regulatory T cell

Intestinal Tregs suppress immune responses through the secretion of inhibitory cytokines such as IL-10, TGF-beta, and IL-35; direct cell-to-cell contact inhibition via CTLA-4 and LAG-3; and the depletion of local IL-2 through high-affinity CD25 receptors (PMID: 21248730, PMID: 30635652).