Unraveling the role of γδ T cells in inflammatory bowel disease: Development and prevention strategies.

Inflammatory bowel diseases (IBD), encompassing ulcerative colitis (UC) and Crohn's disease (CD), are autoimmune disorders characterized by heterogeneous clinical manifestations and dysregulated immune responses. Central to this pathophysiology is the disruption of the intestinal mucosal and epithelial barrier, leading to dysbiosis. Among immune players, γδ (γδ) T-cells have emerged as key regulators of intestinal epithelial homeostasis. These cells, a minor subset of T lymphocytes, are distinguished by their γδ T-cell receptor (TCR) and are capable of rapidly responding to stress signals, pathogens, and tissue damage. γδ T-cells are categorized into subtypes based on their TCR repertoire, tissue distribution, and functional properties, with δ-chain expression defining subsets in humans and γ-chain in mice. In the context of IBD, γδ T-cells contribute to the pathogenesis of both UC and CD, primarily through the production of proinflammatory cytokines, such as IL-17. Furthermore, their interaction with other immune cells and the intestinal epithelium significantly impacts the local immune response and the integrity of the mucosal barrier. Notably, the crosstalk between intestinal microbiota and γδ T-cells is essential for the regulation of these cells, influencing their activation and promoting effective immune responses against bacterial infections. Given their unique immunoregulatory capabilities, γδ T-cells represent promising targets for novel therapeutic strategies aimed at not only alleviating IBD symptoms but also reducing the risk of colorectal cancer, ultimately improving long-term patient outcomes.