IL-21 and IL-21R are not required for development of Th17 cells and autoimmunity in vivo.
Th17 cells have been recognized as the central effectors in organ-related autoimmune diseases. IL-6 is a key factor that reciprocally regulates Th17 and Foxp3(+) Treg differentiation by inhibition of TGF-beta induced Foxp3 and induction of RORgammat, a Th17 lineage-specific transcription factor. Recently IL-21 has been suggested to induce RORgammat and Th17 development in the absence of IL-6. However, the relevance of IL-21 for Th17-dependent inflammatory responses in vivo remains unclear. In this study, we demonstrate that differentiation of IL-17-producing CD4 T cells, their recruitment to inflamed organs, and the development of autoimmune disease was not affected in il21R(-/-) and il21(-/-) mice in models of myelin oligodendrocyte glycoprotein-induced autoimmune encephalitis and autoimmune myocarditis. IL-6 induced Th17 differentiation independent of and much more potently than IL-21 in vitro. These data suggest that IL-6 is sufficient to drive Th17 development and associated autoimmunity in vivo in the absence of IL-21 or IL-21R.
Institute of Integrative Biology, Molecular Biomedicine, ETH Zürich, Zürich, Switzerland.
Ivo
I
Sonderegger
Jan
J
Kisielow
Reto
R
Meier
Cecile
C
King
Manfred
M
Kopf
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D015551:Autoimmunity; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology; D020381:Interleukin-17 / Q000276:immunology* / Q000378:metabolism; D015850:Interleukin-6 / Q000276:immunology* / Q000378:metabolism; D007378:Interleukins / Q000172:deficiency / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009205:Myocarditis / Q000276:immunology; D020721:Nervous System Autoimmune Disease, Experimental / Q000276:immunology; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D053655:Receptors, Interleukin-21 / Q000172:deficiency / Q000276:immunology* / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D000098546:Interleukin-21
D020381:Interleukin-17; D015850:Interleukin-6; D007378:Interleukins; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D053655:Receptors, Interleukin-21; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; C539901:Rorc protein, mouse; D016212:Transforming Growth Factor beta; D000098546:Interleukin-21