Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2018 Feb 19:7:205.
doi: 10.12688/f1000research.13020.1. eCollection 2018.

Update on regulation and effector functions of Th17 cells

Ivy Sandquist  1 , Jay Kolls  1
Affiliations
Review

Update on regulation and effector functions of Th17 cells

Ivy Sandquist et al. F1000Res. .

Abstract

T-helper cells that produce IL-17 are recognized as a significant subset within cell-mediated adaptive immunity. These cells are implicated in both the pathology of inflammatory disorders as well as the clearance of extracellular infections and the maintenance of the microbiota. However, the dynamic nature of this cell type has created controversy in understanding Th17 induction as well as Th17 phenotyping, since these cells may switch from Th17 to Treg or Th17 to Th1 cytokine profiles under certain conditions. This review highlights recent advances in Th17 cells in understanding their role in commensal regulation, sex difference in immune outcomes and the immunology of pregnancy, as well as inventive experimental models that have allowed for an increased understanding of Th17 regulation and induction.

Keywords: CD4+; TH17; regulation.

PubMed Disclaimer

Conflict of interest statement

No competing interests were disclosed.No competing interests were disclosed.No competing interests were disclosed.No competing interests were disclosed.

Figures

Figure 1.
Figure 1.. Upon barrier disruption or attachment of symbionts, APCs release inflammatory cytokines, including IL-23, in response to DAMPs and PAMPs at the site of damage.
IL-23 signaling leads to increased production of IL-22 and G-CSF by Th17 cells as well as increased differentiation of naïve cells into Th17 cells. Neutralization and microbial containment occur at the site of inflammation owing partially to increased antimicrobial peptides and neutrophil recruitment due to IL-22 and G-CSF signaling, respectively. Concurrently, loss of IL-17 receptors at the site of damage leads to loss of IL17R signaling and an increase in free IL-17. The increased free IL-17 works in a positive feedback loop to increase Th17 proliferation near the site of barrier disruption. IL17R signaling where receptors have not been damaged leads to stabilization of the transport protein PigR and increased sIgA transport to the lumen, allowing neutralization of overabundant microbes. Additionally, demonstrated T-cell receptor specificity for commensal microbes leads to increased activity of the Th17 cell type in response to intestinal microbial imbalances. APC, antigen-presenting cell; DAMP, damage-associated molecular pattern molecule; G-CSF, granulocyte-colony-stimulating factor; IL, interleukin; PAMP, pathogen-associated molecular pattern; Th, T helper.
See this image and copyright information in PMC

References

    1. Miossec P, Kolls JK: Targeting IL-17 and T H17 cells in chronic inflammation. Nat Rev Drug Discov. 2012;11(10):763–76. 10.1038/nrd3794 - DOI - PubMed
    1. Chen K, Kolls JK: Interluekin-17A (IL17A). Gene. 2017;614:8–14. 10.1016/j.gene.2017.01.016 - DOI - PMC - PubMed
    1. Weaver CT, Elson CO, Fouser LA, et al. : The Th17 pathway and inflammatory diseases of the intestines, lungs, and skin. Annu Rev Pathol. 2013;8:477–512. 10.1146/annurev-pathol-011110-130318 - DOI - PMC - PubMed
    1. Bettelli E, Carrier Y, Gao W, et al. : Reciprocal developmental pathways for the generation of pathogenic effector T H17 and regulatory T cells. Nature. 2006;441(7090):235–8. 10.1038/nature04753 - DOI - PubMed

    2. F1000 Recommendation

    1. Veldhoen M, Hocking RJ, Atkins CJ, et al. : TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells. Immunity. 2006;24(2):179–89. 10.1016/j.immuni.2006.01.001 - DOI - PubMed

    2. F1000 Recommendation