Stat3 and Stat4 direct development of IL-17-secreting Th cells.
IL-17-secreting CD4(+) T cells are critically involved in inflammatory immune responses. Development of these cells is promoted in vivo and in vitro by IL-23 or TGFbeta1 plus IL-6. Despite growing interest in this inflammatory Th subset, little is known about the transcription factors that are required for their development. We demonstrate that Stat3 is required for programming the TGFbeta1 plus IL-6 and IL-23-stimulated IL-17-secreting phenotype, as well as for RORgammat expression in TGFbeta1 plus IL-6-primed cells. Moreover, retroviral transduction of a constitutively active Stat3 into differentiating T cell cultures enhances IL-17 production from these cells. We further show that Stat4 is partially required for the development of IL-23-, but not TGFbeta1 plus IL-6-primed IL-17-secreting cells, and is absolutely required for IL-17 production in response to IL-23 plus IL-18. The requirements for Stat3 and Stat4 in the development of these IL-17-secreting subsets reveal additional mechanisms in Th cell fate decisions during the generation of proinflammatory cell types.
Mathur
Anubhav N
AN
Department of Pediatrics, Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Chang
Hua-Chen
HC
Zisoulis
Dimitrios G
DG
Stritesky
Gretta L
GL
Yu
Qing
Q
O'Malley
John T
JT
Kapur
Reuben
R
Levy
David E
DE
Kansas
Geoffrey S
GS
Kaplan
Mark H
MH
D000818:Animals; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000494:pharmacology; D020381:Interleukin-17 / Q000096:biosynthesis*; D020382:Interleukin-18 / Q000494:pharmacology; D053759:Interleukin-23 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D050796:STAT3 Transcription Factor / Q000502:physiology*; D050797:STAT4 Transcription Factor / Q000502:physiology*; D018417:Th1 Cells / Q000276:immunology*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology
D020381:Interleukin-17; D020382:Interleukin-18; D053759:Interleukin-23; D015850:Interleukin-6; D050796:STAT3 Transcription Factor; D050797:STAT4 Transcription Factor; C494087:Stat3 protein, mouse; C494091:Stat4 protein, mouse; D053773:Transforming Growth Factor beta1; D018664:Interleukin-12; D007371:Interferon-gamma