Interleukin-2 Signaling via STAT5 Constrains T Helper 17 Cell Generation

• Published in: Immunity (Cambridge, Mass.) Vol. 26; no. 3; pp. 371 - 381
• Main Authors: Laurence, Arian, Tato, Cristina M., Davidson, Todd S., Kanno, Yuka, Chen, Zhi, Yao, Zhengju, Blank, Rebecca B., Meylan, Françoise, Siegel, Richard, Hennighausen, Lothar, Shevach, Ethan M., O'Shea, John J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-03-2007; Elsevier Limited
• Subjects: Animals; Apoptosis; Cell Differentiation - genetics; CELLIMMUNO; Disease; Interleukin-17 - metabolism; Interleukin-2 - genetics; Interleukin-2 - pharmacology; Interleukin-2 - physiology; Lymphocyte Activation - genetics; Lymphocytes; Mice; Mice, Mutant Strains; MOLIMMUNO; Proteins; Rodents; SIGNALING; STAT3 Transcription Factor - genetics; STAT3 Transcription Factor - physiology; STAT5 Transcription Factor - genetics; STAT5 Transcription Factor - physiology; T cell receptors; T-Lymphocytes, Helper-Inducer - drug effects; T-Lymphocytes, Helper-Inducer - immunology; MOLIMMUNO; SIGNALING; CELLIMMUNO
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2007.02.009

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 RORγt 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.