Transcriptomics and proteomics reveal a cooperation between interferon and T-helper 17 cells in neuromyelitis optica

Agnieshka M. Agasing, Qi Wu, Bhuwan Khatri, Nadja Borisow, Klemens Ruprecht, Alexander Ulrich Brandt, Saurabh Gawde, Gaurav Kumar, James L. Quinn, Rose M. Ko, Yang Mao-Draayer, Christopher J. Lessard, Friedemann Paul and Robert C. Axtell ()
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Agnieshka M. Agasing: Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation
Qi Wu: Department of Neurology, University of Michigan Medical School
Bhuwan Khatri: Genes and Human Disease Research Program, Oklahoma Medical Research Foundation
Nadja Borisow: NeuroCure Clinical Research Center and Experimental and Clinical Research Center, Max Delbrueck Center for Molecular Medicine and Charité Universitätsmedizin
Klemens Ruprecht: Department of Neurology with Experimental Neurology, Charité Universitätsmedizin
Alexander Ulrich Brandt: NeuroCure Clinical Research Center and Experimental and Clinical Research Center, Max Delbrueck Center for Molecular Medicine and Charité Universitätsmedizin
Saurabh Gawde: Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation
Gaurav Kumar: Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation
James L. Quinn: Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation
Rose M. Ko: Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation
Yang Mao-Draayer: Department of Neurology, University of Michigan Medical School
Christopher J. Lessard: Genes and Human Disease Research Program, Oklahoma Medical Research Foundation
Friedemann Paul: NeuroCure Clinical Research Center and Experimental and Clinical Research Center, Max Delbrueck Center for Molecular Medicine and Charité Universitätsmedizin
Robert C. Axtell: Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation

Nature Communications, 2020, vol. 11, issue 1, 1-13

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-16625-7

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