Elevated IL-6 expression in CD4 T cells via PKCθ and NF-κB induces Th2 cytokine production

M. Hanief Sofi, Wei Li, Mark Kaplan, Cheong Hee Chang

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

T helper (Th) cell differentiation is a key event to mount an appropriate immune response. Th1 and Th2 cells produce their signature cytokines IFN-γ and IL-4, respectively. However, as we have reported, CD4 T cells selected by MHC class II-expressing thymocytes (T-CD4) produce both Th1 and Th2 type cytokines under Th1 differentiation conditions. Furthermore, the expression of Th2 cytokines in these cells is Stat6 independent. In the current study, we investigated the molecular mechanisms by which CD4 T cells produce Th2 cytokines under the Th1 differentiation condition. We observed that IL-6 is highly expressed in T-CD4 T cells, which is at least partly responsible for Th2 cytokine production by Th1 differentiated cells. The enhanced expression of IL-6 is downstream of constitutive phosphorylation of PKCθ and high NF-κB activity. Neutralizing IL-6, blocking PKCθ phosphorylation, or inhibiting NF-κB translocation diminished Th2 cytokine expression in Th1 cultures. Therefore, our study revealed that autocrine IL-6 production can induce Th2 cytokine production, and that PKCθ and NF-κB are essential components in the induction of IL-6-mediated Th2 development.

Original languageEnglish
Pages (from-to)1443-1450
Number of pages8
JournalMolecular Immunology
Volume46
Issue number7
DOIs
StatePublished - Apr 2009

Fingerprint

Interleukin-6
Cytokines
T-Lymphocytes
Th1 Cells
Phosphorylation
Th2 Cells
Thymocytes
Interleukin-4
Cell Differentiation

Keywords

  • Cytokines
  • Rodents
  • Signal transduction
  • T cells

ASJC Scopus subject areas

  • Molecular Biology
  • Immunology

Cite this

Elevated IL-6 expression in CD4 T cells via PKCθ and NF-κB induces Th2 cytokine production. / Sofi, M. Hanief; Li, Wei; Kaplan, Mark; Chang, Cheong Hee.

In: Molecular Immunology, Vol. 46, No. 7, 04.2009, p. 1443-1450.

Research output: Contribution to journalArticle

Sofi, M. Hanief ; Li, Wei ; Kaplan, Mark ; Chang, Cheong Hee. / Elevated IL-6 expression in CD4 T cells via PKCθ and NF-κB induces Th2 cytokine production. In: Molecular Immunology. 2009 ; Vol. 46, No. 7. pp. 1443-1450.
@article{49ba3c3c33ff4c20a8b32a25d5245a37,
title = "Elevated IL-6 expression in CD4 T cells via PKCθ and NF-κB induces Th2 cytokine production",
abstract = "T helper (Th) cell differentiation is a key event to mount an appropriate immune response. Th1 and Th2 cells produce their signature cytokines IFN-γ and IL-4, respectively. However, as we have reported, CD4 T cells selected by MHC class II-expressing thymocytes (T-CD4) produce both Th1 and Th2 type cytokines under Th1 differentiation conditions. Furthermore, the expression of Th2 cytokines in these cells is Stat6 independent. In the current study, we investigated the molecular mechanisms by which CD4 T cells produce Th2 cytokines under the Th1 differentiation condition. We observed that IL-6 is highly expressed in T-CD4 T cells, which is at least partly responsible for Th2 cytokine production by Th1 differentiated cells. The enhanced expression of IL-6 is downstream of constitutive phosphorylation of PKCθ and high NF-κB activity. Neutralizing IL-6, blocking PKCθ phosphorylation, or inhibiting NF-κB translocation diminished Th2 cytokine expression in Th1 cultures. Therefore, our study revealed that autocrine IL-6 production can induce Th2 cytokine production, and that PKCθ and NF-κB are essential components in the induction of IL-6-mediated Th2 development.",
keywords = "Cytokines, Rodents, Signal transduction, T cells",
author = "Sofi, {M. Hanief} and Wei Li and Mark Kaplan and Chang, {Cheong Hee}",
year = "2009",
month = "4",
doi = "10.1016/j.molimm.2008.12.014",
language = "English",
volume = "46",
pages = "1443--1450",
journal = "Molecular Immunology",
issn = "0161-5890",
publisher = "Elsevier Limited",
number = "7",

}

TY - JOUR

T1 - Elevated IL-6 expression in CD4 T cells via PKCθ and NF-κB induces Th2 cytokine production

AU - Sofi, M. Hanief

AU - Li, Wei

AU - Kaplan, Mark

AU - Chang, Cheong Hee

PY - 2009/4

Y1 - 2009/4

N2 - T helper (Th) cell differentiation is a key event to mount an appropriate immune response. Th1 and Th2 cells produce their signature cytokines IFN-γ and IL-4, respectively. However, as we have reported, CD4 T cells selected by MHC class II-expressing thymocytes (T-CD4) produce both Th1 and Th2 type cytokines under Th1 differentiation conditions. Furthermore, the expression of Th2 cytokines in these cells is Stat6 independent. In the current study, we investigated the molecular mechanisms by which CD4 T cells produce Th2 cytokines under the Th1 differentiation condition. We observed that IL-6 is highly expressed in T-CD4 T cells, which is at least partly responsible for Th2 cytokine production by Th1 differentiated cells. The enhanced expression of IL-6 is downstream of constitutive phosphorylation of PKCθ and high NF-κB activity. Neutralizing IL-6, blocking PKCθ phosphorylation, or inhibiting NF-κB translocation diminished Th2 cytokine expression in Th1 cultures. Therefore, our study revealed that autocrine IL-6 production can induce Th2 cytokine production, and that PKCθ and NF-κB are essential components in the induction of IL-6-mediated Th2 development.

AB - T helper (Th) cell differentiation is a key event to mount an appropriate immune response. Th1 and Th2 cells produce their signature cytokines IFN-γ and IL-4, respectively. However, as we have reported, CD4 T cells selected by MHC class II-expressing thymocytes (T-CD4) produce both Th1 and Th2 type cytokines under Th1 differentiation conditions. Furthermore, the expression of Th2 cytokines in these cells is Stat6 independent. In the current study, we investigated the molecular mechanisms by which CD4 T cells produce Th2 cytokines under the Th1 differentiation condition. We observed that IL-6 is highly expressed in T-CD4 T cells, which is at least partly responsible for Th2 cytokine production by Th1 differentiated cells. The enhanced expression of IL-6 is downstream of constitutive phosphorylation of PKCθ and high NF-κB activity. Neutralizing IL-6, blocking PKCθ phosphorylation, or inhibiting NF-κB translocation diminished Th2 cytokine expression in Th1 cultures. Therefore, our study revealed that autocrine IL-6 production can induce Th2 cytokine production, and that PKCθ and NF-κB are essential components in the induction of IL-6-mediated Th2 development.

KW - Cytokines

KW - Rodents

KW - Signal transduction

KW - T cells

UR - http://www.scopus.com/inward/record.url?scp=62549111295&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=62549111295&partnerID=8YFLogxK

U2 - 10.1016/j.molimm.2008.12.014

DO - 10.1016/j.molimm.2008.12.014

M3 - Article

C2 - 19181387

AN - SCOPUS:62549111295

VL - 46

SP - 1443

EP - 1450

JO - Molecular Immunology

JF - Molecular Immunology

SN - 0161-5890

IS - 7

ER -