ROR{gamma}t Expression and Lymphoid Neogenesis in the Brain of Patients with Secondary Progressive Multiple Sclerosis

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-t (RORt) 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 RORt 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 RORt-positive cells were detected in the meninges of 6 of 12 SPMS cases analyzed. RORt-positive cells were localized in B-cell follicles or aggregates and nearby diffuse meningeal infiltrates, and predominantly co-expressed CD3. Only a few RORt-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 RORt and predominantly CD3, were found in meningeal B-cell follicles from 4 SPMS cases. Rare RORt-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 RORt and IL17 signals, respectively. Thus, there is selective migration or survival of RORt-positive cells in MS patient meninges and an association of these cells with ELS.
Source: Journal of Neuropathology and Experimental Neurology - Category: Neurology Authors: Tags: Original Articles Source Type: research