T helper 17 cell

T helper 17 cells (Th17) are a subset of pro-inflammatory T helper cells defined by their production of interleukin 17 (IL-17). They are related to T regulatory cells and the signals that cause Th17s to differentiate actually inhibit Treg differentiation. However, Th17s are developmentally distinct from Th1 and Th2 lineages. Th17 cells play an important role in maintaining mucosal barriers and contributing to pathogen clearance at mucosal surfaces; such protective and non-pathogenic Th17 cells have been call Treg17 cells. T helper 17 cells (Th17) are a subset of pro-inflammatory T helper cells defined by their production of interleukin 17 (IL-17). They are related to T regulatory cells and the signals that cause Th17s to differentiate actually inhibit Treg differentiation. However, Th17s are developmentally distinct from Th1 and Th2 lineages. Th17 cells play an important role in maintaining mucosal barriers and contributing to pathogen clearance at mucosal surfaces; such protective and non-pathogenic Th17 cells have been call Treg17 cells. They have also been implicated in autoimmune and inflammatory disorders. The loss of Th17 cell populations at mucosal surfaces has been linked to chronic inflammation and microbial translocation. These regulatory Th17 cells are generated by TGF-beta plus IL-6 in vitro. Like conventional regulatory T cells (Treg), induction of regulatory Treg17 cells could play an important role in modulating and preventing certain autoimmune diseases. Treg17 (Regulatory Th17) cells are generated from CD4+ T cells. Transforming growth factor beta (TGF-β), interleukin 6 (IL-6), interleukin 21 (IL-21) and interleukin 23 (IL-23) contribute to Th17 formation in mice and humans. Key factors in the differentiation of Th17 cells are signal transducer and the activator of transcription 3 (Stat3) and retinoic acid receptor-related orphan receptors gamma (RORγ) and alpha (RORα). Th17 cells are differentiated when naive T cells are exposed to the cytokines mentioned above. These cytokines are produced by activated antigen presenting cells (APCs) after contact with pathogens. The Th17 cells can alter their differentiation program ultimately giving rise to either protective or pro-inflammatory pathogenic cells. The protective and non-pathogenic Th17 cells induced by IL-6 and TGF-β are termed as Treg17 cells. The pathogenic Th17 cells are induced by IL-23 and IL-1β. IL-21, produced by Th17 cells themselves, has also been shown to initiate an alternative route for the activation of Th17 populations. Both interferon gamma (IFNγ) and IL-4, the main stimulators of Th1 and Th2 differentiation, respectively, have been shown to inhibit Th17 differentiation. Similar to Th17 cells the Treg17 development depended on the transcription factor Stat3. Th17 cells play a role in adaptive immunity protecting the body against pathogens. However, anti-fungal immunity appears to be limited to particular sites with detrimental effects observed. Their main effector cytokines are IL-17A, IL-17F, IL-21, and IL-22, as well as granulocyte-macrophage colony-stimulating factor (GM-CSF). IL-17 family cytokines (IL-17A and IL-17F) target innate immune cells and epithelial cells, among others, to produce G-CSF and IL-8 (CXCL8), which leads to neutrophil production and recruitment. In this way, Th17 cell lineage appears to be one of the three major subsets of effector T cells, as these cells are involved in regulation of neutrophils, while Th2 cells regulate eosinophils, basophils and mast cells, and Th1 cells regulate macrophages and monocytes. Thus, three T helper cell subsets are able to influence the myeloid part of the immune system, largely responsible for innate defense against pathogens. Treg17 cells with regulatory phenotype with in vivo immune-suppressive properties in the gut have also been identified as rTh17 cells. Treg17 cells produce IL-17 and IL-10 and low level of IL-22 and suppress autoimmune and other immune responses. CD4+ T cells polarized with IL-23 and IL-6 are pathogenic upon adoptive transfer in type 1 diabetes while cells polarized with TGF-beta and IL-6 are not pathogenic., The intracellular aryl hydrocarbon receptor (AhR), which is activated by certain aromatic compounds, is specifically expressed in Treg17 cells. These cells are regulated by IL-23 and TGF-beta. The production of IL-22 in this subset of Th17 cells is regulated by AhR and Treg17 cells are depend on activation of the transcription factor Stat3. In a steady state, TGF-beta and AhR ligands induce low expression of IL-22 along with high expression of AhR, c-MAF, IL-10, and IL-21 that might play a protective role in cell regeneration and host microbiome homeostasis. Th17 cells mediate the regression of tumors in mice, but were also found to promote tumor formation induced by colonic inflammation in mice. Like other T helper cells, Th17 cells closely interact with B cells in response to pathogens. Th17 cells are involved in B cell recruitment through CXCL13 chemokine signaling, and Th17 activity may encourage antibody production.