Regulation of IL-10 and IL-17 mediated experimental autoimmune encephalomyelitis by S-nitrosoglutathione.
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.
['Singh|Inderjit|I|', 'Nath|Narender|N|', 'Saxena|Nishant|N|', 'Singh|Avtar K|AK|', 'Won|Je-Seong|JS|']
D019264:Adoptive Transfer D000818:Animals D015496:CD4-Positive T-Lymphocytes D004681:Encephalomyelitis, Autoimmune, Experimental D056747:Immunomodulation D007371:Interferon-gamma D016753:Interleukin-10 D020381:Interleukin-17 D051379:Mice D008810:Mice, Inbred C57BL D020030:Nitric Oxide Donors D026422:S-Nitrosoglutathione D018417:Th1 Cells D058504:Th17 Cells
IL-10 IL-17 S-Nitrosoglutathione (GSNO) Experimental autoimmune encephalomyelitis (EAE) Adoptive transfer T(H)1 T(H)17