Transcriptional Regulatory Networks in Th17 Cell Differentiation

Overview

Journal Curr Opin Immunol

Publisher Elsevier

Specialty Allergy & Immunology

Date 2009 Mar 31

PMID 19328669

Citations 98

Authors

Liang Zhou

Dan R Littman

Affiliations

Soon will be listed here.

Abstract

Upon encountering antigen in the context of antigen presenting cells, naïve CD4(+) T cells undergo differentiation into effector T helper (Th) cells, which can secrete high levels of cytokines and other immunomodulators to mediate host defense and tissue inflammation. During the past three years, the immunology field has witnessed an explosion of research advances in the biology of Th17 cells, the most recently described subset of T helper cells, which play crucial roles in host immunity and inflammation. Here we review emerging data on transcriptional regulatory networks that govern the differentiation program of Th17 cells, and focus on how the orphan nuclear receptor RORgammat coordinates this process in concert with diverse cytokine-induced transcription factors.

Citing Articles

The protective and pathogenic role of Th17 cell plasticity and function in the tumor microenvironment.

Pan Y, Yang W, Tang B, Wang X, Zhang Q, Li W Front Immunol. 2023; 14:1192303.

PMID: 37457739 PMC: 10339829. DOI: 10.3389/fimmu.2023.1192303.

Immunotherapy targeting plasma ASM is protective in a mouse model of Alzheimer's disease.

Choi B, Park M, Park K, Han W, Yoon H, Jung H Nat Commun. 2023; 14(1):1631.

PMID: 36959217 PMC: 10036484. DOI: 10.1038/s41467-023-37316-z.

T17 cell heterogeneity and its role in tissue inflammation.

Schnell A, Littman D, Kuchroo V Nat Immunol. 2023; 24(1):19-29.

PMID: 36596896 PMC: 10795475. DOI: 10.1038/s41590-022-01387-9.

Deeper insight into the role of IL-17 in the relationship beween hypertension and intestinal physiology.

Yang Z, Wang T, Wang B, Gao H, He C, Shang H J Inflamm (Lond). 2022; 19(1):14.

PMID: 36195874 PMC: 9530412. DOI: 10.1186/s12950-022-00311-0.

Interleukin-17 Family Cytokines in Metabolic Disorders and Cancer.

Meehan E, Wang K Genes (Basel). 2022; 13(9).

PMID: 36140808 PMC: 9498678. DOI: 10.3390/genes13091643.

References

Zhang F, Meng G, Strober W . Interactions among the transcription factors Runx1, RORgammat and Foxp3 regulate the differentiation of interleukin 17-producing T cells. Nat Immunol. 2008; 9(11):1297-306. PMC: 4778724. DOI: 10.1038/ni.1663. View

Park H, Li Z, Yang X, Chang S, Nurieva R, Wang Y . A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat Immunol. 2005; 6(11):1133-41. PMC: 1618871. DOI: 10.1038/ni1261. View

Yang X, Nurieva R, Martinez G, Kang H, Chung Y, Pappu B . Molecular antagonism and plasticity of regulatory and inflammatory T cell programs. Immunity. 2008; 29(1):44-56. PMC: 2630532. DOI: 10.1016/j.immuni.2008.05.007. View

Manel N, Unutmaz D, Littman D . The differentiation of human T(H)-17 cells requires transforming growth factor-beta and induction of the nuclear receptor RORgammat. Nat Immunol. 2008; 9(6):641-9. PMC: 2597394. DOI: 10.1038/ni.1610. View

Veldhoen M, Hirota K, Christensen J, OGarra A, Stockinger B . Natural agonists for aryl hydrocarbon receptor in culture medium are essential for optimal differentiation of Th17 T cells. J Exp Med. 2008; 206(1):43-9. PMC: 2626686. DOI: 10.1084/jem.20081438. View

Egawa T, Eberl G, Taniuchi I, Benlagha K, Geissmann F, Hennighausen L . Genetic evidence supporting selection of the Valpha14i NKT cell lineage from double-positive thymocyte precursors. Immunity. 2005; 22(6):705-16. DOI: 10.1016/j.immuni.2005.03.011. View

Vignali D, Collison L, Workman C . How regulatory T cells work. Nat Rev Immunol. 2008; 8(7):523-32. PMC: 2665249. DOI: 10.1038/nri2343. View

Bettelli E, Carrier Y, Gao W, Korn T, Strom T, Oukka M . Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature. 2006; 441(7090):235-8. DOI: 10.1038/nature04753. View

Veldhoen M, Hocking R, Atkins C, Locksley R, Stockinger B . 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. DOI: 10.1016/j.immuni.2006.01.001. View

10.

Ivanov I, de Llanos Frutos R, Manel N, Yoshinaga K, Rifkin D, Sartor R . Specific microbiota direct the differentiation of IL-17-producing T-helper cells in the mucosa of the small intestine. Cell Host Microbe. 2008; 4(4):337-49. PMC: 2597589. DOI: 10.1016/j.chom.2008.09.009. View

11.

Langowski J, Zhang X, Wu L, Mattson J, Chen T, Smith K . IL-23 promotes tumour incidence and growth. Nature. 2006; 442(7101):461-5. DOI: 10.1038/nature04808. View

12.

Coquet J, Chakravarti S, Smyth M, Godfrey D . Cutting edge: IL-21 is not essential for Th17 differentiation or experimental autoimmune encephalomyelitis. J Immunol. 2008; 180(11):7097-101. DOI: 10.4049/jimmunol.180.11.7097. View

13.

Zheng Y, Valdez P, Danilenko D, Hu Y, Sa S, Gong Q . Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens. Nat Med. 2008; 14(3):282-9. DOI: 10.1038/nm1720. View

14.

Nguyen L, Bradfield C . The search for endogenous activators of the aryl hydrocarbon receptor. Chem Res Toxicol. 2007; 21(1):102-16. PMC: 2572005. DOI: 10.1021/tx7001965. View

15.

Schambach F, Schupp M, Lazar M, Reiner S . Activation of retinoic acid receptor-alpha favours regulatory T cell induction at the expense of IL-17-secreting T helper cell differentiation. Eur J Immunol. 2007; 37(9):2396-9. DOI: 10.1002/eji.200737621. View

16.

Li M, Flavell R . TGF-beta: a master of all T cell trades. Cell. 2008; 134(3):392-404. PMC: 3677783. DOI: 10.1016/j.cell.2008.07.025. View

17.

Ichiyama K, Yoshida H, Wakabayashi Y, Chinen T, Saeki K, Nakaya M . Foxp3 inhibits RORgammat-mediated IL-17A mRNA transcription through direct interaction with RORgammat. J Biol Chem. 2008; 283(25):17003-8. DOI: 10.1074/jbc.M801286200. View

18.

Chen Z, Laurence A, Kanno Y, Pacher-Zavisin M, Zhu B, Tato C . Selective regulatory function of Socs3 in the formation of IL-17-secreting T cells. Proc Natl Acad Sci U S A. 2006; 103(21):8137-42. PMC: 1459629. DOI: 10.1073/pnas.0600666103. View

19.

Quintana F, Basso A, Iglesias A, Korn T, Farez M, Bettelli E . Control of T(reg) and T(H)17 cell differentiation by the aryl hydrocarbon receptor. Nature. 2008; 453(7191):65-71. DOI: 10.1038/nature06880. View

20.

Huber M, Brustle A, Reinhard K, Guralnik A, Walter G, Mahiny A . IRF4 is essential for IL-21-mediated induction, amplification, and stabilization of the Th17 phenotype. Proc Natl Acad Sci U S A. 2008; 105(52):20846-51. PMC: 2634912. DOI: 10.1073/pnas.0809077106. View