Article (Scientific journals)
Targeting prohibitins at the cell surface prevents Th17-mediated autoimmunity.
Buehler, Ulrike; Schulenburg, Katharina; Yurugi, Hajime et al.
2018In The EMBO journal, 37 (16)
Peer reviewed
 

Files


Full Text
7E66A04D-1E5E-49DA-B5DC-B6FDBB93BCDF.pdf
Publisher postprint (1.93 MB)
Request a copy

All documents in ORBilu are protected by a user license.

Send to



Details



Keywords :
CRAF; FOXP3; MAPK; multiple sclerosis; prohibitins
Abstract :
[en] T helper (Th)17 cells represent a unique subset of CD4(+) T cells and are vital for clearance of extracellular pathogens including bacteria and fungi. However, Th17 cells are also involved in orchestrating autoimmunity. By employing quantitative surface proteomics, we found that the evolutionarily conserved prohibitins (PHB1/2) are highly expressed on the surface of both murine and human Th17 cells. Increased expression of PHBs at the cell surface contributed to enhanced CRAF/MAPK activation in Th17 cells. Targeting surface-expressed PHBs on Th17 cells with ligands such as Vi polysaccharide (Typhim vaccine) inhibited CRAF-MAPK pathway, reduced interleukin (IL)-17 expression and ameliorated disease pathology with an increase in FOXP3(+)-expressing Tregs in an animal model for multiple sclerosis (MS). Interestingly, we detected a CD4(+) T cell population with high PHB1 surface expression in blood samples from MS patients in comparison with age- and sex-matched healthy subjects. Our observations suggest a pivotal role for the PHB-CRAF-MAPK signalling axis in regulating the polarization and pathogenicity of Th17 cells and unveil druggable targets in autoimmune disorders such as MS.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Buehler, Ulrike
Schulenburg, Katharina
Yurugi, Hajime
Solman, Maja
Abankwa, Daniel  ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Ulges, Alexander
Tenzer, Stefan
Bopp, Tobias
Thiede, Bernd
Zipp, Frauke
Rajalingam, Krishnaraj
External co-authors :
yes
Language :
English
Title :
Targeting prohibitins at the cell surface prevents Th17-mediated autoimmunity.
Publication date :
2018
Journal title :
The EMBO journal
ISSN :
0261-4189
eISSN :
1460-2075
Volume :
37
Issue :
16
Peer reviewed :
Peer reviewed
Commentary :
(c) 2018 The Authors.
Available on ORBilu :
since 18 January 2019

Statistics


Number of views
122 (4 by Unilu)
Number of downloads
0 (0 by Unilu)

Scopus citations®
 
17
Scopus citations®
without self-citations
16
OpenCitations
 
11
WoS citations
 
15

Bibliography


Similar publications



Contact ORBilu