Signal transduction and Th17 cell differentiation.
The paradigm of effector T helper cell differentiation into either Th1 or Th2 lineages has been notably shaken by the discovery of a third lineage of cells that selectively produce interleukin (IL)-17. Characterization of this new subset, referred to as Th17, has provided exciting new insights into immunoregulation, host defense and the pathogenesis of autoimmune diseases. Additionally, the discovery of this T cell subset has offered a fresh look at such concepts as lineage commitment and terminal differentiation. The transcriptional regulatory events and epigenetic modifications that control these processes are diverse and complex, and despite the rapid pace at which data continue to accumulate, many questions remain to be answered. Here we review our current understanding of the signaling pathways, molecular interactions and transcriptional events that lead to Th17 differentiation and effector function, as well as the epigenetic modifications that accompany them.
O'Shea
John J
JJ
Molecular Immunology and Inflammation Branch, National Institutes of Arthritis, and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Steward-Tharp
Scott M
SM
Laurence
Arian
A
Watford
Wendy T
WT
Wei
Lai
L
Adamson
Adewole S
AS
Fan
Samuel
S
D002454:Cell Differentiation; D006801:Humans; D020381:Interleukin-17 / Q000276:immunology; D016131:Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D015398:Signal Transduction; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology*
D020381:Interleukin-17