T helper 17 cell
Encyclopedia
T helper 17 cells are a subset of T helper cells producing interleukin 17
(IL-17) discovered in 2007. They are considered developmentally distinct from Th1 and Th2 cells and excessive amounts of the cell are thought to play a key role in autoimmune disease
such as multiple sclerosis
(which was previously thought to be caused by Th1 cells), but also psoriasis, autoimmune uveitis, juvenile diabetes, rheumatoid arthritis, and Crohn's disease.
More specifically, they are thought to play a role in inflammation
and tissue injury in these conditions. Th17 cells can cause severe autoimmune diseases, however they serve a very important function in 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 severe lack of Th17 cells may leave the host susceptible to opportunistic infections.
(IL-6), interleukin 21
(IL-21) and interleukin 23
(IL-23) have been implicated in mice and humans. 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, have been shown to negatively regulate Th17 differentiation.
:
Interleukin 17
Interleukin-17 is the founding member of a group of cytokines called the IL-17 family. IL-17A, was originally identified as a transcript from a rodent T-cell hybridoma by Rouvier et al. in 1993...
(IL-17) discovered in 2007. They are considered developmentally distinct from Th1 and Th2 cells and excessive amounts of the cell are thought to play a key role in autoimmune disease
Autoimmunity
Autoimmunity is the failure of an organism to recognize its own constituent parts as self, which allows an immune response against its own cells and tissues. Any disease that results from such an aberrant immune response is termed an autoimmune disease...
such as multiple sclerosis
Multiple sclerosis
Multiple sclerosis is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms...
(which was previously thought to be caused by Th1 cells), but also psoriasis, autoimmune uveitis, juvenile diabetes, rheumatoid arthritis, and Crohn's disease.
More specifically, they are thought to play a role in inflammation
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
and tissue injury in these conditions. Th17 cells can cause severe autoimmune diseases, however they serve a very important function in anti-microbial immunity at epithelial / mucosal barriers. They produce cytokines (such as interleukin 22
Interleukin 22
Interleukin-22 is protein that in humans is encoded by the IL22 gene.IL-22 a member of a group of cytokines called the IL-10 family or IL-10 superfamily , a class of potent mediators of cellular inflammatory responses. It shares use of IL-10R2 in cell signaling with other members of this family,...
) which stimulates epithelial cells to produce anti-microbial proteins to clear out certain types of microbe (such as Candida
Candida (genus)
Candida is a genus of yeasts. Many species are harmless commensals or endosymbionts of animal hosts including humans, but other species, or harmless species in the wrong location, can cause disease. Candida albicans can cause infections in humans and other animals, especially in immunocompromised...
and Staphylococcus
Staphylococcus
Staphylococcus is a genus of Gram-positive bacteria. Under the microscope they appear round , and form in grape-like clusters....
). Thus, a severe lack of Th17 cells may leave the host susceptible to opportunistic infections.
Differentiation
It remains unclear exactly which cytokines contribute to Th17 formation, but transforming growth factor beta (TGF-β), interleukin 6Interleukin 6
Interleukin-6 is a protein that in humans is encoded by the IL6 gene.IL-6 is an interleukin that acts as both a pro-inflammatory and anti-inflammatory cytokine. It is secreted by T cells and macrophages to stimulate immune response, e.g. during infection and after trauma, especially burns or other...
(IL-6), interleukin 21
Interleukin 21
Interleukin-21 is a protein that in humans is encoded by the IL21 gene.Interleukin 21 is a cytokine that has potent regulatory effects on cells of the immune system, including natural killer cells and cytotoxic T cells that can destroy virally infected or cancerous cells...
(IL-21) and interleukin 23
Interleukin 23
Interleukin-23 subunit alpha is a protein that in humans is encoded by the IL23A gene. IL-23 is produced by dendritic cells and macrophages...
(IL-23) have been implicated in mice and humans. 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
STAT3
Signal transducer and activator of transcription 3 also known as STAT3 is a transcription factor which in humans is encoded by the STAT3 gene.- Function :The protein encoded by this gene is a member of the STAT protein family...
) and the retinoic-acid-receptor-related orphan receptors alpha (RORα
RAR-related orphan receptor alpha
RAR-related orphan receptor alpha , also known as NR1F1 is a nuclear receptor that in humans is encoded by the RORA gene.- Function :...
) and gamma (RORγ
RAR-related orphan receptor gamma
RAR-related orphan receptor gamma is a protein that in humans is encoded by the RORC gene. RORγ is member of the nuclear receptor family of transcription factors.- Gene expression :...
). 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
Interferon type II
A sole member makes up the type II IFNs that is called IFN-γ . Mature IFN-γ is an anti-parallel homodimer, which binds to the IFN-γ receptor complex to elicit a signal within its target cell...
(IFNγ) and IL-4
Interleukin 4
Interleukin-4, abbreviated IL-4, is a cytokine that induces differentiation of naive helper T cells to Th2 cells. Upon activation by IL-4, Th2 cells subsequently produce additional IL-4. The cell that initially produces IL-4, thus inducing Th0 differentiation, has not been identified, but recent...
, the main stimulators of Th1 and Th2 differentiation, have been shown to negatively regulate Th17 differentiation.
Functions
On initial characterisation, Th17 cells were broadly implicated in autoimmune disease, and auto-specific Th17 cells were shown to be highly pathologic. A more natural role for Th17 cells is suggested by studies that have demonstrated preferential induction of IL-17 in cases of host infection with various bacterial and fungal species. Th17 cells primarily produce two main members of the IL-17 family, IL-17A and IL-17F, which are involved in the recruitment, activation and migration of neutrophils. These cells also secrete IL-21 and IL-22. Recently, Th17 polarized cells have been shown to mediate the regression of established tumors in mice. Whether the highly inflammatory nature of Th17 cells is sufficient to cause or contribute to carcinogenesis is the subject of current debate.External links
There are some open access Network Protocols for studying Th17 cells at Nature ProtocolsNature Protocols
Nature Protocols, published by the Nature Publishing Group, is an on-line scientific journal publishing methods in a recipe-style format. The journal was launched in June 2006 and the content includes both classical methods and cutting-edge techniques relevant to the study of biological problems...
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