Targeting prohibitins at the cell surface prevents Th17-mediated autoimmunity
| Autor: | Bernd Thiede, Frauke Zipp, Daniel Abankwa, Krishnaraj Rajalingam, Stefan Tenzer, Hajime Yurugi, Katharina Schulenburg, Tobias Bopp, Alexander Ulges, Maja Šolman, Ulrike Buehler |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway Multiple Sclerosis T cell Cell Population Autoimmunity Biology medicine.disease_cause T-Lymphocytes Regulatory General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Mice Prohibitins Rickettsial Vaccines medicine Animals Humans education Extracellular Signal-Regulated MAP Kinases Molecular Biology education.field_of_study General Immunology and Microbiology General Neuroscience Interleukin FOXP3 Forkhead Transcription Factors Articles Cell biology Repressor Proteins 030104 developmental biology medicine.anatomical_structure Th17 Cells Signal transduction HeLa Cells Signal Transduction |
| Zdroj: | The EMBO journal. 37(16) |
| ISSN: | 1460-2075 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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