IL-21 and IL-21R are not required for development of Th17 cells and autoimmunity in vivo.

Abstract

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.

• Authors: Ivo Sonderegger, Jan Kisielow, Reto Meier, Cecile King, Manfred Kopf
• Journal: European journal of immunology (Eur J Immunol) Vol. 38 Issue 7 Pg. 1833-8 (Jul 2008) ISSN: 0014-2980 [Print] Germany
• PMID: 18546146 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-17
• Interleukin-6
• Interleukins
• Nuclear Receptor Subfamily 1, Group F, Member 3
• Receptors, Interleukin-21
• Receptors, Retinoic Acid
• Receptors, Thyroid Hormone
• Rorc protein, mouse
• Transforming Growth Factor beta
• interleukin-21

Topics

• Animals
• Autoimmune Diseases (immunology)
• Autoimmunity
• Disease Models, Animal
• Encephalomyelitis, Autoimmune, Experimental (immunology)
• Interleukin-17 (immunology, metabolism)
• Interleukin-6 (immunology, metabolism)
• Interleukins (deficiency, immunology, metabolism)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, Knockout
• Myocarditis (immunology)
• Nervous System Autoimmune Disease, Experimental (immunology)
• Nuclear Receptor Subfamily 1, Group F, Member 3
• Receptors, Interleukin-21 (deficiency, immunology, metabolism)
• Receptors, Retinoic Acid (metabolism)
• Receptors, Thyroid Hormone (metabolism)
• T-Lymphocytes, Helper-Inducer (immunology, metabolism)
• T-Lymphocytes, Regulatory (immunology, metabolism)
• Transforming Growth Factor beta (metabolism)