T helper 17 cell
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, besides others, the signal transducer and the activator of transcription 3 (Stat3) and the retinoic acid receptor-related orphan receptors gamma (RORγ) and alpha (RORα). 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.
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. Th17 cells mediate the regression of tumors in mice, but were also found to promote tumor formation induced by inflammation of the colon in mice.
Th17 cells, particularly auto-specific Th17 cells, are associated with autoimmune disease such as multiple sclerosis, rheumatoid arthritis, and psoriasis. Th17 overactivation against autoantigen will cause type 3 immune complex and complement-mediated hypersensitivity. Rheumatoid arthritis or Arthus reaction belong to this category.
Bone erosion caused by mature osteoclast cells is common in patients with rheumatoid arthritis. Activated T helper cells such as Th1, Th2, and Th17 are found in the synovial cavity during the time of inflammation due to rheumatoid arthritis. The known mechanisms associated with the differentiation of osteoclast precursors into mature osteoclasts involve the signaling molecules produced by immune-associated cells, as well as the direct cell to cell contact of osteoblasts and osteoclast precursors. However, it has been suggested that Th17 can also play a more major role in osteoclast differentiation via cell to cell contact with osteoclast precursors.
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- Singh A, Yamamoto M, Ruan J, Choi JY, Gauvreau GM, Olek S, Hoffmueller U, Carlsten C, FitzGerald JM, Boulet LP, O'Byrne PM, Tebbutt SJ. (24 Jun 2014). "Th17/Treg ratio derived using DNA methylation analysis is associated with the late phase asthmatic response.". Allergy Asthma Clin Immunol 10 (1): 32. doi:10.1186/1710-1492-10-32. PMC 4078401. PMID 24991220.