Stat3 and Stat4 direct development of IL-17-secreting Th cells

Anubhav N. Mathur, Hua Chen Chang, Dimitrios G. Zisoulis, Gretta L. Stritesky, Qing Yu, John T. O'Malley, Reuben Kapur, David E. Levy, Geoffrey S. Kansas, Mark Kaplan

Research output: Contribution to journalArticle

389 Citations (Scopus)

Abstract

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 TGFβ1 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 TGFβ1 plus IL-6 and IL-23-stimulated IL-17-secreting phenotype, as well as for RORγt expression in TGFβ1 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 TGFβ1 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.

Original languageEnglish
Pages (from-to)4901-4907
Number of pages7
JournalJournal of Immunology
Volume178
Issue number8
StatePublished - Apr 15 2007

Fingerprint

Interleukin-17
Interleukin-23
Interleukin-6
T-Lymphocytes
Interleukin-18
Transcription Factors
Cell Culture Techniques
Phenotype

ASJC Scopus subject areas

  • Immunology

Cite this

Mathur, A. N., Chang, H. C., Zisoulis, D. G., Stritesky, G. L., Yu, Q., O'Malley, J. T., ... Kaplan, M. (2007). Stat3 and Stat4 direct development of IL-17-secreting Th cells. Journal of Immunology, 178(8), 4901-4907.

Stat3 and Stat4 direct development of IL-17-secreting Th cells. / Mathur, Anubhav N.; Chang, Hua Chen; Zisoulis, Dimitrios G.; Stritesky, Gretta L.; Yu, Qing; O'Malley, John T.; Kapur, Reuben; Levy, David E.; Kansas, Geoffrey S.; Kaplan, Mark.

In: Journal of Immunology, Vol. 178, No. 8, 15.04.2007, p. 4901-4907.

Research output: Contribution to journalArticle

Mathur, AN, Chang, HC, Zisoulis, DG, Stritesky, GL, Yu, Q, O'Malley, JT, Kapur, R, Levy, DE, Kansas, GS & Kaplan, M 2007, 'Stat3 and Stat4 direct development of IL-17-secreting Th cells', Journal of Immunology, vol. 178, no. 8, pp. 4901-4907.
Mathur AN, Chang HC, Zisoulis DG, Stritesky GL, Yu Q, O'Malley JT et al. Stat3 and Stat4 direct development of IL-17-secreting Th cells. Journal of Immunology. 2007 Apr 15;178(8):4901-4907.
Mathur, Anubhav N. ; Chang, Hua Chen ; Zisoulis, Dimitrios G. ; Stritesky, Gretta L. ; Yu, Qing ; O'Malley, John T. ; Kapur, Reuben ; Levy, David E. ; Kansas, Geoffrey S. ; Kaplan, Mark. / Stat3 and Stat4 direct development of IL-17-secreting Th cells. In: Journal of Immunology. 2007 ; Vol. 178, No. 8. pp. 4901-4907.
@article{ce4774bc54e14a30813f51243a4c2a81,
title = "Stat3 and Stat4 direct development of IL-17-secreting Th cells",
abstract = "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 TGFβ1 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 TGFβ1 plus IL-6 and IL-23-stimulated IL-17-secreting phenotype, as well as for RORγt expression in TGFβ1 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 TGFβ1 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.",
author = "Mathur, {Anubhav N.} and Chang, {Hua Chen} and Zisoulis, {Dimitrios G.} and Stritesky, {Gretta L.} and Qing Yu and O'Malley, {John T.} and Reuben Kapur and Levy, {David E.} and Kansas, {Geoffrey S.} and Mark Kaplan",
year = "2007",
month = "4",
day = "15",
language = "English",
volume = "178",
pages = "4901--4907",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "8",

}

TY - JOUR

T1 - Stat3 and Stat4 direct development of IL-17-secreting Th cells

AU - Mathur, Anubhav N.

AU - Chang, Hua Chen

AU - Zisoulis, Dimitrios G.

AU - Stritesky, Gretta L.

AU - Yu, Qing

AU - O'Malley, John T.

AU - Kapur, Reuben

AU - Levy, David E.

AU - Kansas, Geoffrey S.

AU - Kaplan, Mark

PY - 2007/4/15

Y1 - 2007/4/15

N2 - 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 TGFβ1 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 TGFβ1 plus IL-6 and IL-23-stimulated IL-17-secreting phenotype, as well as for RORγt expression in TGFβ1 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 TGFβ1 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.

AB - 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 TGFβ1 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 TGFβ1 plus IL-6 and IL-23-stimulated IL-17-secreting phenotype, as well as for RORγt expression in TGFβ1 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 TGFβ1 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.

UR - http://www.scopus.com/inward/record.url?scp=34247122412&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34247122412&partnerID=8YFLogxK

M3 - Article

C2 - 17404271

AN - SCOPUS:34247122412

VL - 178

SP - 4901

EP - 4907

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 8

ER -