TLR2 stimulation regulates the balance between regulatory T cell and Th17 function: a novel mechanism of reduced regulatory T cell function in multiple sclerosis
CD4+CD25hi FOXP3+ regulatory T cells (Tregs) maintain tolerance to self-Ags. Their defective function is involved in the pathogenesis of multiple sclerosis (MS), an inflammatory demyelinating disease of the CNS. However, the mechanisms of such defective function are poorly understood. Recently, we r...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
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American Association of Immunologists
2015
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| Online Access: | https://eprints.nottingham.ac.uk/35716/ |
| _version_ | 1848795144956936192 |
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| author | Nyirenda, Mukanthu H. Morandi, Elena Vinkemeier, Uwe Constantin-Teodosiu, Dumitru Drinkwater, Sophie Mee, Maureen King, Lloyd Podda, Giulio Zhang, Guang-Xian Ghaemmaghami, Amir Constantinescu, Cris S. Bar-Or, Amit Gran, Bruno |
| author_facet | Nyirenda, Mukanthu H. Morandi, Elena Vinkemeier, Uwe Constantin-Teodosiu, Dumitru Drinkwater, Sophie Mee, Maureen King, Lloyd Podda, Giulio Zhang, Guang-Xian Ghaemmaghami, Amir Constantinescu, Cris S. Bar-Or, Amit Gran, Bruno |
| author_sort | Nyirenda, Mukanthu H. |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | CD4+CD25hi FOXP3+ regulatory T cells (Tregs) maintain tolerance to self-Ags. Their defective function is involved in the pathogenesis of multiple sclerosis (MS), an inflammatory demyelinating disease of the CNS. However, the mechanisms of such defective function are poorly understood. Recently, we reported that stimulation of TLR2, which is preferentially expressed by human Tregs, reduces their suppressive function and skews them into a Th17-like phenotype. In this study, we tested the hypothesis that TLR2 activation is involved in reduced Treg function in MS. We found that Tregs from MS patients expressed higher levels of TLR2 compared with healthy controls, and stimulation with the synthetic lipopeptide Pam3Cys, an agonist of TLR1/2, reduced Treg function and induced Th17 skewing in MS patient samples more than in healthy controls. These data provide a novel mechanism underlying diminished Treg function in MS. Infections that activate TLR2 in vivo (specifically through TLR1/2 heterodimers) could shift the Treg/Th17 balance toward a proinflammatory state in MS, thereby promoting disease activity and progression. |
| first_indexed | 2025-11-14T19:27:25Z |
| format | Article |
| id | nottingham-35716 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:27:25Z |
| publishDate | 2015 |
| publisher | American Association of Immunologists |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-357162020-04-29T15:12:38Z https://eprints.nottingham.ac.uk/35716/ TLR2 stimulation regulates the balance between regulatory T cell and Th17 function: a novel mechanism of reduced regulatory T cell function in multiple sclerosis Nyirenda, Mukanthu H. Morandi, Elena Vinkemeier, Uwe Constantin-Teodosiu, Dumitru Drinkwater, Sophie Mee, Maureen King, Lloyd Podda, Giulio Zhang, Guang-Xian Ghaemmaghami, Amir Constantinescu, Cris S. Bar-Or, Amit Gran, Bruno CD4+CD25hi FOXP3+ regulatory T cells (Tregs) maintain tolerance to self-Ags. Their defective function is involved in the pathogenesis of multiple sclerosis (MS), an inflammatory demyelinating disease of the CNS. However, the mechanisms of such defective function are poorly understood. Recently, we reported that stimulation of TLR2, which is preferentially expressed by human Tregs, reduces their suppressive function and skews them into a Th17-like phenotype. In this study, we tested the hypothesis that TLR2 activation is involved in reduced Treg function in MS. We found that Tregs from MS patients expressed higher levels of TLR2 compared with healthy controls, and stimulation with the synthetic lipopeptide Pam3Cys, an agonist of TLR1/2, reduced Treg function and induced Th17 skewing in MS patient samples more than in healthy controls. These data provide a novel mechanism underlying diminished Treg function in MS. Infections that activate TLR2 in vivo (specifically through TLR1/2 heterodimers) could shift the Treg/Th17 balance toward a proinflammatory state in MS, thereby promoting disease activity and progression. American Association of Immunologists 2015-05-15 Article PeerReviewed Nyirenda, Mukanthu H., Morandi, Elena, Vinkemeier, Uwe, Constantin-Teodosiu, Dumitru, Drinkwater, Sophie, Mee, Maureen, King, Lloyd, Podda, Giulio, Zhang, Guang-Xian, Ghaemmaghami, Amir, Constantinescu, Cris S., Bar-Or, Amit and Gran, Bruno (2015) TLR2 stimulation regulates the balance between regulatory T cell and Th17 function: a novel mechanism of reduced regulatory T cell function in multiple sclerosis. Journal of Immunology, 194 (12). pp. 5761-5774. ISSN 1550-6606 http://dx.doi.org/10.4049/jimmunol.1400472 doi:10.4049/jimmunol.1400472 doi:10.4049/jimmunol.1400472 |
| spellingShingle | Nyirenda, Mukanthu H. Morandi, Elena Vinkemeier, Uwe Constantin-Teodosiu, Dumitru Drinkwater, Sophie Mee, Maureen King, Lloyd Podda, Giulio Zhang, Guang-Xian Ghaemmaghami, Amir Constantinescu, Cris S. Bar-Or, Amit Gran, Bruno TLR2 stimulation regulates the balance between regulatory T cell and Th17 function: a novel mechanism of reduced regulatory T cell function in multiple sclerosis |
| title | TLR2 stimulation regulates the balance between regulatory T cell and Th17 function: a novel mechanism of reduced regulatory T cell function in multiple sclerosis |
| title_full | TLR2 stimulation regulates the balance between regulatory T cell and Th17 function: a novel mechanism of reduced regulatory T cell function in multiple sclerosis |
| title_fullStr | TLR2 stimulation regulates the balance between regulatory T cell and Th17 function: a novel mechanism of reduced regulatory T cell function in multiple sclerosis |
| title_full_unstemmed | TLR2 stimulation regulates the balance between regulatory T cell and Th17 function: a novel mechanism of reduced regulatory T cell function in multiple sclerosis |
| title_short | TLR2 stimulation regulates the balance between regulatory T cell and Th17 function: a novel mechanism of reduced regulatory T cell function in multiple sclerosis |
| title_sort | tlr2 stimulation regulates the balance between regulatory t cell and th17 function: a novel mechanism of reduced regulatory t cell function in multiple sclerosis |
| url | https://eprints.nottingham.ac.uk/35716/ https://eprints.nottingham.ac.uk/35716/ https://eprints.nottingham.ac.uk/35716/ |