Two-sided roles of IL-27: Induction of Th1 differentiation on naive CD4+ T cells versus suppression of proinflammatory cytokine production including IL-23-induced IL-17 on activated CD4+ T cells partially through STAT3-dependent mechanism

Takeru Yoshimura, Atsunobu Takeda, Shinjiro Hamano, Yoshiyuki Miyazaki, Ichiko Kinjyo, Tatsuro Ishibashi, Akihiko Yoshimura, Hiroki Yoshida

Research output: Contribution to journalArticle

179 Citations (Scopus)

Abstract

Recent lines of evidence have demonstrated that IL-27, a newly identified IL-12-related cytokine, has two apparently conflicting roles in immune responses: one as an initiator of Th1 responses and the other as an attenuator of inflammatory cytokine production. Although the BL-27-mediated Th1 initiation mechanism has been elucidated, little is known about the molecular basis for the suppression of cytokine production. In the present study, we demonstrated that IL-27 suppressed the production of various proinflammatory cytokines by fully activated CD4+ T cells while it had no effect on the cytokine production by CD4+ T cells at early phases of activation. IL-27 also suppressed IL-17 production by activated CD4+ T cells, thereby counteracting IL-23, another IL-12-related cytokine with proinflammatory effects. In fully activated CD4+ T cells, STAT3 was preferentially activated by IL-27 stimulation, whereas both STAT1 and 3 were activated by IL-27 in early activated CD4+ T cells. Lack of STAT3 in fully activated cells impaired the suppressive effects of IL-27. These data indicated that the preferential activation of STAT3 in fully activated CD4+ T cells plays an important role in the cytokine suppression by IL-27/WSX-1.

Original languageEnglish
Pages (from-to)5377-5385
Number of pages9
JournalJournal of Immunology
Volume177
Issue number8
DOIs
Publication statusPublished - Oct 15 2006

Fingerprint

Interleukin-27
Interleukin-23
Interleukin-17
Cytokines
T-Lymphocytes
Interleukin-12

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Two-sided roles of IL-27 : Induction of Th1 differentiation on naive CD4+ T cells versus suppression of proinflammatory cytokine production including IL-23-induced IL-17 on activated CD4+ T cells partially through STAT3-dependent mechanism. / Yoshimura, Takeru; Takeda, Atsunobu; Hamano, Shinjiro; Miyazaki, Yoshiyuki; Kinjyo, Ichiko; Ishibashi, Tatsuro; Yoshimura, Akihiko; Yoshida, Hiroki.

In: Journal of Immunology, Vol. 177, No. 8, 15.10.2006, p. 5377-5385.

Research output: Contribution to journalArticle

@article{12f2d8cc32944951b2d888bd2a4be428,
title = "Two-sided roles of IL-27: Induction of Th1 differentiation on naive CD4+ T cells versus suppression of proinflammatory cytokine production including IL-23-induced IL-17 on activated CD4+ T cells partially through STAT3-dependent mechanism",
abstract = "Recent lines of evidence have demonstrated that IL-27, a newly identified IL-12-related cytokine, has two apparently conflicting roles in immune responses: one as an initiator of Th1 responses and the other as an attenuator of inflammatory cytokine production. Although the BL-27-mediated Th1 initiation mechanism has been elucidated, little is known about the molecular basis for the suppression of cytokine production. In the present study, we demonstrated that IL-27 suppressed the production of various proinflammatory cytokines by fully activated CD4+ T cells while it had no effect on the cytokine production by CD4+ T cells at early phases of activation. IL-27 also suppressed IL-17 production by activated CD4+ T cells, thereby counteracting IL-23, another IL-12-related cytokine with proinflammatory effects. In fully activated CD4+ T cells, STAT3 was preferentially activated by IL-27 stimulation, whereas both STAT1 and 3 were activated by IL-27 in early activated CD4+ T cells. Lack of STAT3 in fully activated cells impaired the suppressive effects of IL-27. These data indicated that the preferential activation of STAT3 in fully activated CD4+ T cells plays an important role in the cytokine suppression by IL-27/WSX-1.",
author = "Takeru Yoshimura and Atsunobu Takeda and Shinjiro Hamano and Yoshiyuki Miyazaki and Ichiko Kinjyo and Tatsuro Ishibashi and Akihiko Yoshimura and Hiroki Yoshida",
year = "2006",
month = "10",
day = "15",
doi = "10.4049/jimmunol.177.8.5377",
language = "English",
volume = "177",
pages = "5377--5385",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "8",

}

TY - JOUR

T1 - Two-sided roles of IL-27

T2 - Induction of Th1 differentiation on naive CD4+ T cells versus suppression of proinflammatory cytokine production including IL-23-induced IL-17 on activated CD4+ T cells partially through STAT3-dependent mechanism

AU - Yoshimura, Takeru

AU - Takeda, Atsunobu

AU - Hamano, Shinjiro

AU - Miyazaki, Yoshiyuki

AU - Kinjyo, Ichiko

AU - Ishibashi, Tatsuro

AU - Yoshimura, Akihiko

AU - Yoshida, Hiroki

PY - 2006/10/15

Y1 - 2006/10/15

N2 - Recent lines of evidence have demonstrated that IL-27, a newly identified IL-12-related cytokine, has two apparently conflicting roles in immune responses: one as an initiator of Th1 responses and the other as an attenuator of inflammatory cytokine production. Although the BL-27-mediated Th1 initiation mechanism has been elucidated, little is known about the molecular basis for the suppression of cytokine production. In the present study, we demonstrated that IL-27 suppressed the production of various proinflammatory cytokines by fully activated CD4+ T cells while it had no effect on the cytokine production by CD4+ T cells at early phases of activation. IL-27 also suppressed IL-17 production by activated CD4+ T cells, thereby counteracting IL-23, another IL-12-related cytokine with proinflammatory effects. In fully activated CD4+ T cells, STAT3 was preferentially activated by IL-27 stimulation, whereas both STAT1 and 3 were activated by IL-27 in early activated CD4+ T cells. Lack of STAT3 in fully activated cells impaired the suppressive effects of IL-27. These data indicated that the preferential activation of STAT3 in fully activated CD4+ T cells plays an important role in the cytokine suppression by IL-27/WSX-1.

AB - Recent lines of evidence have demonstrated that IL-27, a newly identified IL-12-related cytokine, has two apparently conflicting roles in immune responses: one as an initiator of Th1 responses and the other as an attenuator of inflammatory cytokine production. Although the BL-27-mediated Th1 initiation mechanism has been elucidated, little is known about the molecular basis for the suppression of cytokine production. In the present study, we demonstrated that IL-27 suppressed the production of various proinflammatory cytokines by fully activated CD4+ T cells while it had no effect on the cytokine production by CD4+ T cells at early phases of activation. IL-27 also suppressed IL-17 production by activated CD4+ T cells, thereby counteracting IL-23, another IL-12-related cytokine with proinflammatory effects. In fully activated CD4+ T cells, STAT3 was preferentially activated by IL-27 stimulation, whereas both STAT1 and 3 were activated by IL-27 in early activated CD4+ T cells. Lack of STAT3 in fully activated cells impaired the suppressive effects of IL-27. These data indicated that the preferential activation of STAT3 in fully activated CD4+ T cells plays an important role in the cytokine suppression by IL-27/WSX-1.

UR - http://www.scopus.com/inward/record.url?scp=33749515631&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33749515631&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.177.8.5377

DO - 10.4049/jimmunol.177.8.5377

M3 - Article

C2 - 17015723

AN - SCOPUS:33749515631

VL - 177

SP - 5377

EP - 5385

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 8

ER -