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| Item Type: | Article |
|---|---|
| Title: | Transcriptomics and proteomics reveal a cooperation between interferon and T-helper 17 cells in neuromyelitis optica |
| Creators Name: | Agasing, A.M. and Wu, Q. and Khatri, B. and Borisow, N. and Ruprecht, K. and Brandt, A.U. and Gawde, S. and Kumar, G. and Quinn, J.L. and Ko, R.M. and Mao-Draayer, Y. and Lessard, C.J. and Paul, F. and Axtell, R.C. |
| Abstract: | Type I interferon (IFN-I) and T helper 17 (TH17) drive pathology in neuromyelitis optica spectrum disorder (NMOSD) and in TH17-induced experimental autoimmune encephalomyelitis (TH17-EAE). This is paradoxical because the prevalent theory is that IFN-I inhibits TH17 function. Here we report that a cascade involving IFN-I, IL-6 and B cells promotes TH17-mediated neuro-autoimmunity. In NMOSD, elevated IFN-I signatures, IL-6 and IL-17 are associated with severe disability. Furthermore, IL-6 and IL-17 levels are lower in patients on anti-CD20 therapy. In mice, IFN-I elevates IL-6 and exacerbates TH17-EAE. Strikingly, IL-6 blockade attenuates disease only in mice treated with IFN-I. By contrast, B-cell-deficiency attenuates TH17-EAE in the presence or absence of IFN-I treatment. Finally, IFN-I stimulates B cells to produce IL-6 to drive pathogenic TH17 differentiation in vitro. Our data thus provide an explanation for the paradox surrounding IFN-I and TH17 in neuro-autoimmunity, and may have utility in predicting therapeutic response in NMOSD. |
| Keywords: | Autoimmunity, B-Lymphocytes, Experimental Encephalomyelitis Autoimmune, Gene Expression Profiling, Interferon Type I, Interleukin-17, Interleukin-6, Neuromyelitis Optica, Proteomics, Th17 Cells, Animals, Mice |
| Source: | Nature Communications |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Volume: | 11 |
| Number: | 1 |
| Page Range: | 2856 |
| Date: | 5 June 2020 |
| Official Publication: | https://doi.org/10.1038/s41467-020-16625-7 |
| PubMed: | View item in PubMed |
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