IL-9 Controls Central Nervous System Autoimmunity by Suppressing GM-CSF Production.

Abstract

Multiple sclerosis and experimental autoimmune encephalomyelitis (EAE) are inflammatory diseases of the CNS in which Th17 cells play a major role in the disease pathogenesis. Th17 cells that secrete GM-CSF are pathogenic and drive inflammation of the CNS. IL-9 is a cytokine with pleiotropic functions, and it has been suggested that it controls the pathogenic inflammation mediated by Th17 cells, and IL-9R-/- mice develop more severe EAE compared with wild-type counterparts. However, the underlying mechanism by which IL-9 suppresses EAE has not been clearly defined. In this study, we investigated how IL-9 modulates EAE development. By using mice knockout for IL-9R, we show that more severe EAE in IL-9R-/- mice correlates with increased numbers of GM-CSF+ CD4+ T cells and inflammatory dendritic cells (DCs) in the CNS. Furthermore, DCs from IL-9R-/- mice induced more GM-CSF production by T cells and exacerbated EAE upon adoptive transfer than did wild-type DCs. Our results suggest that IL-9 reduces autoimmune neuroinflammation by suppressing GM-CSF production by CD4+ T cells through the modulation of DCs.

• Authors: Satoshi Yoshimura, Rodolfo Thome, Shingo Konno, Elisabeth R Mari, Javad Rasouli, Daniel Hwang, Alexandra Boehm, Yanhua Li, Guang-Xian Zhang, Bogoljub Ciric, Abdolmohamad Rostami
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 204 Issue 3 Pg. 531-539 (02 01 2020) ISSN: 1550-6606 [Electronic] United States
• PMID: 31852750 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 by The American Association of Immunologists, Inc.

Chemical References

• Inflammation Mediators
• Interleukin-9
• Receptors, Interleukin-9
• Granulocyte-Macrophage Colony-Stimulating Factor

Topics

• Adoptive Transfer
• Animals
• Autoimmunity
• Cells, Cultured
• Central Nervous System (physiology)
• Dendritic Cells (immunology)
• Disease Models, Animal
• Encephalomyelitis, Autoimmune, Experimental (immunology)
• Granulocyte-Macrophage Colony-Stimulating Factor (metabolism)
• Humans
• Inflammation Mediators (metabolism)
• Interleukin-9 (metabolism)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Multiple Sclerosis (immunology)
• Receptors, Interleukin-9 (genetics)
• Th17 Cells (immunology)