IL-22 is expressed by Th17 cells in an IL-23-dependent fashion, but not required for the development of autoimmune encephalomyelitis.
Lately, IL-17-secreting Th cells have received an overwhelming amount of attention and are now widely held to be the major pathogenic population in autoimmune diseases. In particular, IL-22-secreting Th17 cells were shown to specifically mark the highly pathogenic population of self-reactive T cells in experimental autoimmune encephalomyelitis (EAE). As IL-17A itself was found to only play a minor role during the development of EAE, IL-22 is now postulated to contribute to the pathogenic function of Th17 cells. The goal of this study was to determine the role and function of IL-22 during the development of CNS autoimmunity in vivo. We found that CNS-invading encephalitogenic Th17 cells coexpress IL-22 and that IL-22 is specifically induced by IL-23 in autoimmune-pathogenic CD4+ T cells in a time- and dose-dependent manner. We next generated IL-22-/- mice, which--in contrast to the prediction that expression of inflammatory cytokines by CNS-invading T cells inevitably confers pathogenic function--turned out to be fully susceptible to EAE. Taken together, we show that self-reactive Th cells coexpress IL-17 and IL-22, but that the latter also does not appear to be directly involved in autoimmune pathogenesis of the CNS.
Neuroimmunology Unit, Department of Neurology, University Hospital Zurich, Zurich, Switzerland.
Katharina
K
Kreymborg
Ruth
R
Etzensperger
Laure
L
Dumoutier
Stefan
S
Haak
Angelita
A
Rebollo
Thorsten
T
Buch
Frank L
FL
Heppner
Jean-Christophe
JC
Renauld
Burkhard
B
Becher
D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology; D015870:Gene Expression; D018390:Gene Targeting; D020381:Interleukin-17 / Q000378:metabolism*; D053759:Interleukin-23 / Q000235:genetics / Q000378:metabolism*; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D000097043:Interleukin-22
D020381:Interleukin-17; D053759:Interleukin-23; D007378:Interleukins; D000097043:Interleukin-22