RORγt Expression and Lymphoid Neogenesis in the Brain of Patients with Secondary Progressive Multiple Sclerosis
Autor: | Barbara Rosicarelli, Caterina Veroni, Francesca Aloisi, Barbara Serafini, Camilla Reali, Ling Zhou |
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Rok vydání: | 2016 |
Předmět: |
Adult
Male 0301 basic medicine Pathology medicine.medical_specialty CD3 Gene Expression Pathology and Forensic Medicine 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Immune system Cell Movement RAR-related orphan receptor gamma medicine Humans Lymphocytes Laser capture microdissection B-Lymphocytes biology Multiple sclerosis Interleukin-17 Innate lymphoid cell Brain General Medicine Middle Aged Multiple Sclerosis Chronic Progressive Nuclear Receptor Subfamily 1 Group F Member 3 medicine.disease 030104 developmental biology Lymphatic system Neurology biology.protein Female Neurology (clinical) Interleukin 17 030217 neurology & neurosurgery |
Zdroj: | Journal of Neuropathology & Experimental Neurology. 75:877-888 |
ISSN: | 1554-6578 0022-3069 |
DOI: | 10.1093/jnen/nlw063 |
Popis: | Ectopic B-cell follicle-like structures (ELS) are found in the meninges of patients with secondary progressive multiple sclerosis (SPMS). Because cells expressing the transcriptional regulator retinoic acid receptor-related orphan receptor-γt (RORγt) and producing interleukin 17 (IL17), e.g. T helper 17 cells and lymphoid tissue inducer (LTi) cells, have been implicated in the formation of ELS, we studied RORγt and IL17 expression in brain tissue from patients with SPMS an assessed their relationships to immune infiltrates and meningeal ELS. By immunohistochemistry, small numbers of RORγt-positive cells were detected in the meninges of 6 of 12 SPMS cases analyzed. RORγt-positive cells were localized in B-cell follicles or aggregates and nearby diffuse meningeal infiltrates, and predominantly co-expressed CD3. Only a few RORγt-positive, CD3-negative cells were observed, suggesting the presence of group 3 innate lymphoid cells, which comprise the LTi cell subset. Some IL17-positive cells, co-expressing in part RORγt and predominantly CD3, were found in meningeal B-cell follicles from 4 SPMS cases. Rare RORγt-positive and IL17-positive cells were detected in white matter. Gene expression analysis of laser dissected meningeal infiltrates and white matter lesions confirmed low frequencies and virtual absence of RORγt and IL17 signals, respectively. Thus, there is selective migration or survival of RORγt-positive cells in MS patient meninges and an association of these cells with ELS. |
Databáze: | OpenAIRE |
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