Journal
AMERICAN JOURNAL OF PATHOLOGY
Volume 178, Issue 2, Pages 794-802Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.ajpath.2010.10.043
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Funding
- Medical Research Council (UK and DK)
- European Commission
- Neuropromise
- Sybilla
- Danish MS Society
- Lundbeck Foundation
- Novo Nordisk
- Naomi Brayson Foundation
- Ministry of Defence, UK
- Deutsche Forschungsgemeinschaft (DFG) [FR1720/1-1]
- MRC
- DFG [FR1720/3]
- Oxford Biomedical Research Centre, part of the UK National Institute for Health Research
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IL-17 producing CD4(+) T cells (Th-17) contribute to the pathogenesis of experimental autoimmune encephalomyelitis and are associated with active disease in multiple sclerosis (MS). In addition to IL-17, Th-17 cells can also express IL-21, IL-22, and IL-6 under Th-17 polarizing conditions (IL-6 and transforming growth factor-beta). In this study we investigated IL-21 and IL-21 receptor (IL-21R) expression in MS lesions by in situ hybridization and immunohistochemistry. We detected strongly IL-21(+) infiltrating cells predominantly in acute but also in chronic active white matter MS lesions in which IL-21 expression was restricted to CD4(+) cells. In contrast, IL-21R was much more broadly distributed on CD4(+), CD19(+), and CD8(+) lymphocytes but not major histocompatibility complex class-II+ macrophages/microglia. Interestingly, in cortical areas we detected both IL-21 and IL-21R expression by neurons. These findings suggest role(s) for IL-21 in both the acute and chronic stages of MS via direct effects on T and B lymphocytes and, demonstrated for the first time, also on neurons. (Am J Pathol 2011, 178:794-802; DOI: 10.1016/j.ajpath.2010.10.043)
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