Interleukin-2 signaling via STAT5 constrains T helper 17 cell generation.
Recent work has identified a new subset of effector T cells that produces interleukin (IL)-17 known as T helper 17 (Th17) cells, which is involved in the pathophysiology of inflammatory diseases and is thought to be developmentally related to regulatory T (Treg) cells. Because of its importance for Treg cells, we examined the role of IL-2 in Th17 generation and demonstrate that a previously unrecognized aspect of IL-2 function is to constrain IL-17 production. Genetic deletion or antibody blockade of IL-2 promoted differentiation of the Th17 cell subset. Whereas STAT3 appeared to be a key positive regulator of RORgammat and IL-17 expression, absence of IL-2 or disruption of its signaling by deletion of the transcription factor STAT5 resulted in enhanced Th17 cell development. We conclude that in addition to the promotion of activation-induced cell death of lymphocytes and the generation of Treg cells, inhibition of Th17 polarization appears to be an important function of IL-2.
Laurence
Arian
A
Molecular Immunology and Inflammation Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Tato
Cristina M
CM
Davidson
Todd S
TS
Kanno
Yuka
Y
Chen
Zhi
Z
Yao
Zhengju
Z
Blank
Rebecca B
RB
Meylan
Françoise
F
Siegel
Richard
R
Hennighausen
Lothar
L
Shevach
Ethan M
EM
O'shea
John J
JJ
D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation / Q000235:genetics; D020381:Interleukin-17 / Q000378:metabolism*; D007376:Interleukin-2 / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D008213:Lymphocyte Activation / Q000235:genetics*; D051379:Mice; D008817:Mice, Mutant Strains; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000502:physiology; D050799:STAT5 Transcription Factor / Q000235:genetics / Q000502:physiology*; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology*
D020381:Interleukin-17; D007376:Interleukin-2; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor