Regulation of IL-10 and IL-17 mediated experimental autoimmune encephalomyelitis by S-nitrosoglutathione.

Abstract

In this study, we investigated IL-10 and IL-17 specific immunomodulatory potential of S-nitrosoglutathione (GSNO), a physiological nitric oxide carrier molecule, in experimental autoimmune encephalomyelitis (EAE). In active EAE model, GSNO treatment attenuated EAE severity and splenic CD4+ T cells isolated from these mice exhibited decreased IL-17 expression without affecting the IFN-γ expression compared to the cells from untreated EAE mice. Similarly, adoptive transfer of these cells to nave mice resulted in reduction in IL-17 expression in the spinal cords of recipient mice with milder EAE severity. CD4+ T cells isolated from GSNO treated EAE mice, as compared to untreated EAE mice, still expressed lower levels of IL-17 under TH17 skewing conditions, but expressed similar levels of IFN-γ under TH1 skewing condition. Interestingly, under both TH17 and TH1 skewing condition, CD4+ T cells isolated from GSNO treated EAE mice, as compared to untreated EAE mice, expressed higher levels of IL-10 and adoptive transfer of these TH17 and TH1 skewed cells seemingly exhibited milder EAE disease. In addition, adoptive transfer of CD4+ T cells from GSNO treated EAE mice to active EAE mice also ameliorated EAE disease with induction of spinal cord expression of IL-10 and reduction in of IL-17, thus suggesting the participation of IL-10 mechanism in GSNO mediated immunomodulation. GSNO treatment of mice passively immunized with CD4+ T cells either from GSNO treated EAE mice or untreated mice further ameliorated EAE disease, supporting efficacy of GSNO for prophylaxis and therapy in EAE. Overall, these data document a modulatory role of GSNO in IL-17/IL-10 axis of EAE and other autoimmune diseases.

• Authors: Inderjit Singh, Narender Nath, Nishant Saxena, Avtar K Singh, Je-Seong Won
• Journal: Immunobiology (Immunobiology) Vol. 223 Issue 10 Pg. 549-554 (10 2018) ISSN: 1878-3279 [Electronic] Netherlands
• PMID: 29960806 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2018 Elsevier GmbH. All rights reserved.

Chemical References

• IL10 protein, mouse
• Il17a protein, mouse
• Interleukin-17
• Nitric Oxide Donors
• Interleukin-10
• S-Nitrosoglutathione
• Interferon-gamma

Topics

• Adoptive Transfer
• Animals
• CD4-Positive T-Lymphocytes (drug effects, immunology, transplantation)
• Encephalomyelitis, Autoimmune, Experimental (immunology, therapy)
• Immunomodulation
• Interferon-gamma (metabolism)
• Interleukin-10 (metabolism)
• Interleukin-17 (metabolism)
• Mice
• Mice, Inbred C57BL
• Nitric Oxide Donors (pharmacology)
• S-Nitrosoglutathione (pharmacology)
• Th1 Cells (drug effects, immunology, transplantation)
• Th17 Cells (drug effects, immunology, transplantation)