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Review
. 2012 Feb 1;13(2):113-20.
doi: 10.1038/embor.2011.248.

Regulation and function of innate and adaptive interleukin-17-producing cells

Keiji Hirota  1 , Helena Ahlfors, João H Duarte, Brigitta Stockinger
Affiliations
Review

Regulation and function of innate and adaptive interleukin-17-producing cells

Keiji Hirota et al. EMBO Rep. .

Abstract

Interleukin-17 (IL-17)-mediated immune responses play a crucial role in the mucosal host defence against microbial and fungal pathogens. However, the chronic activation of IL-17-producing T helper cells can cause autoimmune disease. In addition, recent studies have highlighted key roles of innate cell-mediated IL-17 responses in various inflammatory settings. Besides inflammation, there have also been intriguing findings regarding the involvement of IL-17 responses in the pathogenesis of cardiovascular diseases and tumour formation. Here, we discuss the latest discoveries in regulation and function of innate and adaptive IL-17-producing cells.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Figure 1
Figure 1
Location of IL-17-producing cell types. There are characteristic populations of homeostatic IL-17-producing cell types in different mucosal tissues. Upon inflammation, these cells act in their resident tissue or migrate to other tissues to combat infection. For example, LN CD4+ TH17 cells can give rise to inflammatory CD4+ TH17 cells that migrate to many tissues in the body. ILC, innate lymphoid cell; iNKT, invariant natural killer T cell; LN, lymph node.
Figure 2
Figure 2
Transcriptional regulation of the IL-17 programme. Members of various transcription factor families are implicated in the regulation of IL-17 transcription either directly (solid line) or indirectly (dashed line). Green indicates positive regulation and red negative regulation. AhR, aryl hydrocarbon receptor; Batf, basic leucine zipper transcription factor, ATF-like; HIF, hypoxia-inducible factor; IκB, inhibitor of NF-κB; IKK, inhibitor of NF-κB kinase; IRF, interferon response factor; LXR, liver X receptor; mTORC, mammalian target of rapamycin complex; NF-κB, nuclear factor κB; PPAR, peroxisome proliferator-activated receptor; RelB, v-rel reticuloendotheliosis viral oncogene homologue B; ROR, retinoid-related orphan nuclear receptor; STAT, signal transducer and activator of transcription; TCF, T-cell-specific transcription factor.
Figure 3
Figure 3
Defects and mutations resulting in mucocutaneous candidiasis. Candida albicans is recognized by dectin 1/2 in dendritic cells, which induces the CARD9-mediated transcription of IL-23. IL-23 is recognized by IL-23R, which is expressed by TH17, innate lymphocyte and γδT cells. This induces IL-17A and IL-17F expression, which modulate the immune response by inducing the expression of antimicrobial peptides and chemokines through binding to IL-17RA. TH17 differentiation and IL-17 cytokine expression is positively regulated by STAT3, whereas STAT1 activation antagonizes TH17 cell differentiation. Mucocutaneous candidiasis is caused by various defects in this immune response pathway, including (i) IL-17RA deficiency, (ii) autoantibodies for IL-17, (iii) lack of expression of IL-17F, (iv) mutations resulting in the dominant-negative form of STAT3, (v) expression of a hyperactivated (Act) form of STAT1, or (vi) CARD9 deficiency. CARD, caspase recruitment domain family; DC, dendritic cell; Dec, dectin; IL, interleukin; ILC, innate lymphocyte; STAT, signal transducer and activator of transcription; TH, T helper.
None
João H Duarte, Helena Ahlfors, Brigitta Stockinger & Keiji Hirota
See this image and copyright information in PMC

References

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