Interleukin 27 negatively regulates the development of interleukin 17-producing T helper cells during chronic inflammation of the central nervous system

Jason S Stumhofer; Arian Laurence; Emma H Wilson; Elaine Huang; Cristina M Tato; Leanne M Johnson; Alejandro V Villarino; Qiulong Huang; Akihiko Yoshimura; David Sehy; Christiaan J M Saris; John J O'Shea; Lothar Hennighausen; Matthias Ernst; Christopher A Hunter

doi:10.1038/ni1376

Interleukin 27 negatively regulates the development of interleukin 17-producing T helper cells during chronic inflammation of the central nervous system

Nat Immunol. 2006 Sep;7(9):937-45. doi: 10.1038/ni1376. Epub 2006 Aug 13.

Authors

Jason S Stumhofer¹, Arian Laurence, Emma H Wilson, Elaine Huang, Cristina M Tato, Leanne M Johnson, Alejandro V Villarino, Qiulong Huang, Akihiko Yoshimura, David Sehy, Christiaan J M Saris, John J O'Shea, Lothar Hennighausen, Matthias Ernst, Christopher A Hunter

Affiliation

¹ Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6008, USA.

PMID: 16906166
DOI: 10.1038/ni1376

Abstract

Studies have focused on the events that influence the development of interleukin 17 (IL-17)-producing T helper cells (T(H)-17 cells) associated with autoimmunity, such as experimental autoimmune encephalitis, but relatively little is known about the cytokines that antagonize T(H)-17 cell effector responses. Here we show that IL-27 receptor-deficient mice chronically infected with Toxoplasma gondii developed severe neuroinflammation that was CD4+ T cell dependent and was associated with a prominent IL-17 response. In vitro, treatment of naive primary T cells with IL-27 suppressed the development T(H)-17 cells induced by IL-6 and transforming growth factor-beta, which was dependent on the intracellular signaling molecule STAT1 but was independent of inhibition of IL-6 signaling mediated by the suppressor protein SOCS3. Thus IL-27, a potent inhibitor of T(H)-17 cell development, may be a useful target for treating inflammatory diseases mediated by these cells.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
CD4 Antigens / analysis
Central Nervous System / immunology
Central Nervous System / parasitology
Encephalitis / immunology
Encephalitis / parasitology
Encephalitis / pathology
Interleukin-17 / analysis*
Interleukin-6 / genetics
Interleukin-6 / metabolism
Interleukins / genetics
Interleukins / pharmacology
Interleukins / physiology*
Lymphocyte Activation* / genetics
Mice
Mice, Knockout
Receptors, Cytokine / drug effects
Receptors, Interleukin
STAT1 Transcription Factor / genetics
STAT1 Transcription Factor / metabolism
Suppressor of Cytokine Signaling 3 Protein
Suppressor of Cytokine Signaling Proteins / metabolism
T-Lymphocytes, Helper-Inducer / drug effects
T-Lymphocytes, Helper-Inducer / immunology*
Toxoplasma*
Toxoplasmosis, Cerebral / immunology*
Toxoplasmosis, Cerebral / pathology

Substances

CD4 Antigens
Il27 protein, mouse
Il27ra protein, mouse
Interleukin-17
Interleukin-6
Interleukins
Receptors, Cytokine
Receptors, Interleukin
STAT1 Transcription Factor
Socs3 protein, mouse
Stat1 protein, mouse
Suppressor of Cytokine Signaling 3 Protein
Suppressor of Cytokine Signaling Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding