Transforming growth factor-β induces development of the TH17 lineage View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2006-05

AUTHORS

Paul R Mangan, Laurie E Harrington, Darrell B O'Quinn, Whitney S Helms, Daniel C Bullard, Charles O Elson, Robin D Hatton, Sharon M Wahl, Trenton R Schoeb, Casey T Weaver

ABSTRACT

A new lineage of effector CD4+ T cells characterized by production of interleukin (IL)-17, the T-helper-17 (T(H)17) lineage, was recently described based on developmental and functional features distinct from those of classical T(H)1 and T(H)2 lineages. Like T(H)1 and T(H)2, T(H)17 cells almost certainly evolved to provide adaptive immunity tailored to specific classes of pathogens, such as extracellular bacteria. Aberrant T(H)17 responses have been implicated in a growing list of autoimmune disorders. T(H)17 development has been linked to IL-23, an IL-12 cytokine family member that shares with IL-12 a common subunit, IL-12p40 (ref. 8). The IL-23 and IL-12 receptors also share a subunit, IL-12Rbeta1, that pairs with unique, inducible components, IL-23R and IL-12Rbeta2, to confer receptor responsiveness. Here we identify transforming growth factor-beta (TGF-beta) as a cytokine critical for commitment to T(H)17 development. TGF-beta acts to upregulate IL-23R expression, thereby conferring responsiveness to IL-23. Although dispensable for the development of IL-17-producing T cells in vitro and in vivo, IL-23 is required for host protection against a bacterial pathogen, Citrobacter rodentium. The action of TGF-beta on naive T cells is antagonized by interferon-gamma and IL-4, thus providing a mechanism for divergence of the T(H)1, T(H)2 and T(H)17 lineages. More... »

PAGES

231-234

Journal

TITLE

Nature

ISSUE

7090

VOLUME

441

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nature04754

DOI

http://dx.doi.org/10.1038/nature04754

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1043278106

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/16648837


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