title: RORγt Expression and Lymphoid Neogenesis in the Brain of Patients with Secondary Progressive Multiple Sclerosis.
abstract: 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.
authors.affiliation: From the Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, Rome, Italy (BS, BR, CV, FA) and GlaxoSmithKline Shanghai Research and Development Center, Zhangjiang Hi-Tech Park, TAU, Pudong, China, Neuroscience Shanghai (LZ, CR).
authors.forename: Barbara
authors.initials: B
authors.lastname: Serafini
authors.affiliation: From the Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, Rome, Italy (BS, BR, CV, FA) and GlaxoSmithKline Shanghai Research and Development Center, Zhangjiang Hi-Tech Park, TAU, Pudong, China, Neuroscience Shanghai (LZ, CR).
authors.forename: Barbara
authors.initials: B
authors.lastname: Rosicarelli
authors.affiliation: From the Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, Rome, Italy (BS, BR, CV, FA) and GlaxoSmithKline Shanghai Research and Development Center, Zhangjiang Hi-Tech Park, TAU, Pudong, China, Neuroscience Shanghai (LZ, CR).
authors.forename: Caterina
authors.initials: C
authors.lastname: Veroni
authors.affiliation: From the Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, Rome, Italy (BS, BR, CV, FA) and GlaxoSmithKline Shanghai Research and Development Center, Zhangjiang Hi-Tech Park, TAU, Pudong, China, Neuroscience Shanghai (LZ, CR).
authors.forename: Ling
authors.initials: L
authors.lastname: Zhou
authors.affiliation: From the Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, Rome, Italy (BS, BR, CV, FA) and GlaxoSmithKline Shanghai Research and Development Center, Zhangjiang Hi-Tech Park, TAU, Pudong, China, Neuroscience Shanghai (LZ, CR).
authors.forename: Camilla
authors.initials: C
authors.lastname: Reali
authors.affiliation: From the Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, Rome, Italy (BS, BR, CV, FA) and GlaxoSmithKline Shanghai Research and Development Center, Zhangjiang Hi-Tech Park, TAU, Pudong, China, Neuroscience Shanghai (LZ, CR). francesca.aloisi@iss.it.
authors.forename: Francesca
authors.initials: F
authors.lastname: Aloisi
mesh_terms: D000328:Adult; D001402:B-Lymphocytes / Q000378:metabolism*; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002465:Cell Movement / Q000502:physiology; D005260:Female; D015870:Gene Expression; D006801:Humans; D020381:Interleukin-17 / Q000096:biosynthesis / Q000235:genetics; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D020381:Interleukin-17; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; C539900:RORC protein, human
keywords: Ectopic lymphoid structures; Group 3 innate lymphoid cells; Interleukin-17; Laser capture microdissection.; Meninges; Multiple sclerosis; Retinoic acid receptor-related orphan receptor-γt