T helper 17 cell
They create inflammation and tissue injury in autoimmune disease such as multiple sclerosis (which was previously thought to be caused by Th1 cells), psoriasis, autoimmune uveitis, juvenile diabetes, rheumatoid arthritis, and Crohn's disease.
Their normal role is to provide anti-microbial immunity at epithelial / mucosal barriers. They produce cytokines (such as interleukin 22) which stimulates epithelial cells to produce anti-microbial proteins to clear out certain types of microbe (such as Candida and Staphylococcus). Thus, a lack of Th17 cells leaves the host susceptible to opportunistic infections.
It has recently been questioned, however, whether TGF-β is involved at all in humans, and it is assumed that interleukin 1β may also play a role. Other proteins involved in their differentiation are signal transducer and activator of transcription 3 (STAT3) and the retinoic-acid-receptor-related orphan receptors alpha (RORα) and gamma (RORγ). Effector cytokines associated with this cell type are IL-17, IL-21 and IL-22.
Activation of precursor T helper cells in the presence of TGF-β and IL-6 is thought to drive differentiation of Th17 cells in the mouse. Aside from a cytokine environment, it is unclear whether any other elements of the initial activation of Th17 cells differ from those of other T helper cells. It has been suggested that IL-23 is involved in the expansion of established Th17 populations, but this cytokine alone does not induce differentiation of naive T-cell precursors into this cell type. IL-21, a cytokine produced by Th17 cells themselves, has also been shown to initiate an alternative route for the activation of Th17 populations. In humans, a combination of TGF-β, IL-1β and IL-23 induces Th17 differentiation from naive T cells. 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, particularly auto-specific Th17 cells, are associated with autoimmune disease. The Th17 effector cells are triggered by IL-6 and TGF beta or IL-23 and IL-1beta. Their main effector cytokines are IL-17a, IL-21, and IL-22. The main Th17 effector cells are neutrophils as well as IgM/IgA B cells, and IL-17 CD4 T cells. The key Th17 transcription factors are STAT3 and RORg. 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 beta are termed as Treg17 cells. The pathogenic Th17 cells are induced by IL-23 and IL-1 beta. TH17 cells can activate neutrophils to kill extracellular bacteria and fungi. Th17 cells may attack cancers, but this is debated.
The original function of Th17 cells is to protect the body against bacteria and fungi. Though Th17 cells are implicated in anti-fungal immunity, it is thought to be limited to particular sites with detrimental effects observed. Th17 cells produce two main members of the IL-17 family, IL-17A and IL-17F, which cause recruitment, activation and migration of neutrophils. They also secrete IL-21 and IL-22. Th17 cells mediate the regression of tumors in mice.
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There are some open access Network Protocols for studying Th17 cells at Nature Protocols:
- Egwuagu, Charles; Yu, Cheng-Rong; Amadi-Obi, Ahjoku; Liu, Xuebin; Mahdi, Rashid; Lee, Yun Sang (2007). "TH17 cells contribute to uveitis and scleritis and are inhibited by IL-27/STAT1 in the retina (3) Western Blot Analysis". Nature Protocols. doi:10.1038/nprot.2007.382.
- Egwuagu, Charles; Yu, Cheng-Rong; Amadi-Obi, Ahjoku; Liu, Xuebin; Mahdi, Rashid; Lee, Yun Sang (2007). "TH17 cells contribute to uveitis and scleritis and are inhibited by IL-27/STAT1 in the retina (4) Confocal microscopy". Nature Protocols. doi:10.1038/nprot.2007.383.
- Egwuagu, Charles; Yu, Cheng-Rong; Amadi-Obi, Ahjoku; Liu, Xuebin; Mahdi, Rashid; Lee, Yun Sang (2007). "TH17 cells contribute to uveitis and scleritis and are inhibited by IL-27/STAT1 in the retina (5) Chromatin immunoprecipitation". Nature Protocols. doi:10.1038/nprot.2007.384.