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

Nat Commun. 2020 Jun 5;11(1):2856. doi: 10.1038/s41467-020-16625-7.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Autoimmunity
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • Encephalomyelitis, Autoimmune, Experimental / genetics
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Female
  • Gene Expression Profiling
  • Humans
  • Interferon Type I / immunology*
  • Interleukin-17 / immunology
  • Interleukin-17 / metabolism
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Male
  • Mice
  • Middle Aged
  • Neuromyelitis Optica / genetics
  • Neuromyelitis Optica / immunology*
  • Proteomics
  • Th17 Cells / immunology*


  • IL6 protein, human
  • Interferon Type I
  • Interleukin-17
  • Interleukin-6
  • interleukin-6, mouse