Functional Plasticity of Th17 Cells: Implications in Gastrointestinal Tract Function

Abstract

The gastrointestinal tract is an active player of the human immune system, participating in the innate and adaptive immune responses, keeping the homeostasis of the human being in a healthy status. However, most intestinal conditions are associated with an altered immune response, which implies the activation of CD4(+) T helper (Th) cells. Based on their cytokine secretion, transcription factor expression and immunological functions, the differentiated Th cells were initially subdivided into different lineages: Th1 (that express the transcription factor T-box (T-bet), secrete interferon (IFN)-γ and protect the host against intracellular infections) and Th2 (that express GATA binding protein 3 (GATA-3), secrete interleukin (IL)-4, IL-5 and IL-13, and mediate host defense against helminths). Later, a new subset was identified, the Th17, which selectively produces IL-17A and is crucial for host defense against extracellular pathogens. More recently, a functional plasticity between the Th1 and Th17 lineages has been described, a process sometimes controversial that seems to play a key role in different inflammatory conditions, including those affecting the gastrointestinal system. This review will summarize the current knowledge regarding the regulation and functional role of Th17 cells in the gut, focusing on these newly identified features of this T cell subset, including plasticity, their relationship with regulatory T cells and their heterogeneity in the inflammatory microenvironment. A better understanding of these issues is critical to elucidate the role of Th17 cells in intestine immunity, and so for the design of novel therapeutic approaches for intestinal diseases specifically targeting Th17 cells.

Sodium Chloride Aggravates Arthritis via Th17 Polarization

“…Similar to the in vitro experiments, the high-salt diet promoted intestinal IL-17 production in CIA mice. IL-17 is primarily secreted from Th17 cells, although there are a few cell populations that express IL-17 in the intestine 20. Therefore, the presence of IL-17 in the intestinal tract of CIA mice fed a high-salt diet may indicate that the salt component promotes Th17 differentiation in the intestines.…”

TH17 predominant T‐cell responses in radiation‐induced bowel disease are modulated by treatment with adipose‐derived mesenchymal stromal cells

“…Localized irradiation induces epithelial breakdown, immune cell accumulation, and activation of various compartments of the colon, leading to the secretion of several pro‐inflammatory molecules, including IL1β and TGFβ. These cytokines have been implicated in TH17 differentiation and could explain the increase of IL17 after irradiation . Various studies have analysed the critical role of IL17 in the development of pathologies.…”

Phosphatase Wip1 as a new therapeutic target for intestinal ischemia-reperfusion injury

“…The resistance to intestinal I/R injury in IL-17A-depleted mice and IL-17A knock-out mice [30] indicated that targeting IL-17A to eliminate the higher number of infiltrating neutrophils into local tissues may be a promising therapy for I/R injury. However, as mentioned above, IL-17A is crucial for effective immune responses against commensal bacteria and pathogens in the intestine [31,32]. The simple depletion of IL-17A may induce severe side effects such as infection and bacterial translocation [31,33] and limit clinical trials.…”