Transcriptomics and proteomics reveal a cooperation between interferon and T-helper 17 cells in neuromyelitis optica
| Autor: | Saurabh Gawde, Alexander U. Brandt, James L. Quinn, Klemens Ruprecht, Agnieshka M. Agasing, Christopher J. Lessard, Yang Mao-Draayer, Nadja Borisow, Bhuwan Khatri, Qi Wu, Gaurav Kumar, Friedemann Paul, Robert C. Axtell, Rose M. Ko |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
Proteomics 0301 basic medicine Encephalomyelitis General Physics and Astronomy Autoimmunity medicine.disease_cause Transcriptome Mice 0302 clinical medicine Interferon T-helper 17 cells lcsh:Science B-Lymphocytes Multidisciplinary Interleukin-17 Neuromyelitis Optica Experimental autoimmune encephalomyelitis hemic and immune systems Middle Aged Interferon Type I Female medicine.drug Adult Encephalomyelitis Autoimmune Experimental Science Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences medicine Animals Humans Neuromyelitis optica Interleukin-6 business.industry Gene Expression Profiling Interleukins General Chemistry medicine.disease In vitro eye diseases Blockade 030104 developmental biology Immunology Th17 Cells lcsh:Q business Neurological disorders 030217 neurology & neurosurgery |
| Zdroj: | Nature Communications, Vol 11, Iss 1, Pp 1-13 (2020) Nature Communications |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-020-16625-7 |
| Popis: | 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. Type I IFN has apposing effects in neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS). Here the authors perform molecular profiling of NMOSD patients and mouse mechanistic experiments of neuro-inflammation to show that IFN-I stimulates pathogenic Th17 via IL-6 production by B cells. |
| Databáze: | OpenAIRE |
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