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

Agasing, A.M.; Wu, Q.; Khatri, B.; Borisow, N.; Ruprecht, K.; Brandt, A.U.; Gawde, S.; Kumar, G.; Quinn, J.L.; Ko, R.M.; Mao-Draayer, Y.; Lessard, C.J.; Paul, F.; Axtell, R.C.

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

Tools

Preview	PDF (Original Article) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader 2MB
	Other (Supplementary Information) 14MB

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., Wu, Q., Khatri, B., Borisow, N., Ruprecht, K., Brandt, A.U., Gawde, S., Kumar, G., Quinn, J.L., Ko, R.M., Mao-Draayer, Y., Lessard, C.J., 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

Repository Staff Only: item control page

Download Statistics

Downloads

Downloads per month over past year