Interleukin 27 negatively regulates the development of interleukin 17-producing T helper cells during chronic inflammation of the central nervous system.
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.
Stumhofer
Jason S
JS
Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6008, USA.
Laurence
Arian
A
Wilson
Emma H
EH
Huang
Elaine
E
Tato
Cristina M
CM
Johnson
Leanne M
LM
Villarino
Alejandro V
AV
Huang
Qiulong
Q
Yoshimura
Akihiko
A
Sehy
David
D
Saris
Christiaan J M
CJ
O'Shea
John J
JJ
Hennighausen
Lothar
L
Ernst
Matthias
M
Hunter
Christopher A
CA
D000818:Animals; D015704:CD4 Antigens / Q000032:analysis; D002490:Central Nervous System / Q000276:immunology / Q000469:parasitology; D004660:Encephalitis / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D020381:Interleukin-17 / Q000032:analysis*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D018121:Receptors, Cytokine / Q000187:drug effects; D018123:Receptors, Interleukin; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology*; D014122:Toxoplasma; D016781:Toxoplasmosis, Cerebral / Q000276:immunology* / Q000473:pathology
D015704:CD4 Antigens; C486767:Il27 protein, mouse; C484747:Il27ra protein, mouse; D020381:Interleukin-17; D015850:Interleukin-6; D007378:Interleukins; D018121:Receptors, Cytokine; D018123:Receptors, Interleukin; D050794:STAT1 Transcription Factor; C491411:Socs3 protein, mouse; C494080:Stat1 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins