T helper 17 cell

T helper 17 cell

T helper 17 cells (Th17) are a subset of T helper cells producing interleukin 17. They are considered developmentally distinct from Th1 and Th2 cells and are thought to play a key role in autoimmune disease.cite journal
author=Harrington LE, Hatton RD, Mangan PR, "et al" |title=Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages |journal=Nat. Immunol. |volume=6 |issue=11 |pages=1123–32 |year=2005 |month=Nov |pmid=16200070 |doi=10.1038/ni1254 |url=] [cite journal |author=Stockinger B, Veldhoen M |title=Differentiation and function of Th17 T cells |journal=Curr. Opin. Immunol. |volume=19 |issue=3 |pages=281–6 |year=2007 |pmid=17433650] More specifically, they are thought to play a role in tissue injury in these conditions.cite journal |author=Steinman L |title=A brief history of T(H)17, the first major revision in the T(H)1/T(H)2 hypothesis of T cell-mediated tissue damage |journal=Nat. Med. |volume=13 |issue=2 |pages=139–45 |year=2007 |month=February |pmid=17290272 |doi=10.1038/nm1551 |url=http://dx.doi.org/10.1038/nm1551]

It remains unclear which cytokines exactly contribute to Th17 formation, but transforming growth factor beta (TGF-β), interleukin 6 (IL-6), interleukin 21 (IL-21) and interleukin 23 (IL-23) have been implicated in mice and humans.cite journal |author=Dong C |title=TH17 cells in development: an updated view of their molecular identity and genetic programming |journal=Nat. Rev. Immunol. |volume=8 |issue=5 |pages=337–48 |year=2008 |month=May |pmid=18408735 |doi=10.1038/nri2295 |url=http://dx.doi.org/10.1038/nri2295] cite journal |author=Manel N, Unutmaz D, Littman DR |title=The differentiation of human T(H)-17 cells requires transforming growth factor-beta and induction of the nuclear receptor RORgammat |journal=Nat. Immunol. |volume=9 |issue=6 |pages=641–9 |year=2008 |month=June |pmid=18454151 |doi=10.1038/ni.1610 |url=] 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 RORγ. Effector cytokines associated with this cell type are IL-17, IL-21 and IL-22.cite journal |author=Ouyang W, Kolls JK, Zheng Y |title=The biological functions of T helper 17 cell effector cytokines in inflammation |journal=Immunity |volume=28 |issue=4 |pages=454–67 |year=2008 |month=April |pmid=18400188 |doi=10.1016/j.immuni.2008.03.004 |url=http://linkinghub.elsevier.com/retrieve/pii/S1074-7613(08)00119-2]

Differentiation

Activation of precursor T helper cells in the presence of TGF-beta and IL-6 is thought to drive differentiation of Th17 cells in the mouse. Aside from 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 that cytokine alone does not induce differentiation of naive T-cell precursors into that cell type.cite journal
author=Bettelli E, Carrier Y, Gao W, "et al"
title=Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells
journal=Nature
volume=441
issue=7090
pages=235–8
year=2006
pmid=16648838
doi=10.1038/nature04753] IL-21, a cytokine produced by Th17 cells themselves, has also been shown to initiate an alternative route for the activation of Th17 populations.cite journal
author=Korn T, Bettelli E, Gao W, "et al" |title=IL-21 initiates an alternative pathway to induce proinflammatory T(H)17 cells |journal=Nature |volume=448 |issue=7152 |pages=484–7 |year=2007 |month=Jul |pmid=17581588 |doi=10.1038/nature05970 |url=] In humans, a combination of TGF-beta, 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 negatively regulate Th17 differentiation.

Functions

On initial characterisation, Th17 cells were broadly implicated in autoimmune disease and auto-specific Th17 were shown to be highly pathogenic. A more natural role for Th17 cells is suggested by studies which have demonstrated preferential induction of IL-17 in cases of host infection with various bacterial and fungal species. Th17 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.

References

External links

There are some open access Network Protocols for studying TH17 cells at Nature Protocols:
* [http://www.natureprotocols.com/2007/08/30/th17_cells_contribute_to_uveit_2.php TH17 cells contribute to uveitis and scleritis and are inhibited by IL-27/STAT1 in the retina - Western Blot Analysis]
* [http://www.natureprotocols.com/2007/08/31/th17_cells_contribute_to_uveit_3.php TH17 cells contribute to uveitis and scleritis and are inhibited by IL-27/STAT1 in the retina - Confocal microscopy]
* [http://www.natureprotocols.com/2007/08/31/th17_cells_contribute_to_uveit_4.php TH17 cells contribute to uveitis and scleritis and are inhibited by IL-27/STAT1 in the retina - Chromatin immunoprecipitation]


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