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标题：A TLR/CD44 axis regulates T cell trafficking in experimental and human multiple sclerosis
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作者：Maria Tredicine ; Chiara Camponeschi ; Davide Pirolli 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2022
卷号：25
期号：2
页码：1-26
DOI：10.1016/j.isci.2022.103763
语种：English
出版社：Elsevier
摘要：SummaryIn the pathogenesis of autoimmune disorders, the modulation of leukocytes′ trafficking plays a central role, still poorly understood. Here, we focused on the effect of TLR2 ligands in trafficking of T helper cells through reshuffling ofCD44isoforms repertoire. Concurrently, strain background and TLR2 haplotype affected Wnt/β-catenin signaling pathway and expression of splicing factors. During EAE, mCD44v9-v10was specifically enriched in the forebrain and showed an increased ability to bind stably to osteopontin. Similarly, we observed that hCD44v7was highly enriched in cells of cerebrospinal fluid from MS patients with active lesions. Moreover, TLRs engagement modulated the composition of CD44 variants also in human T helper cells, supporting the hypothesis that pathogens or commensals, through TLRs, in turn modulate the repertoire ofCD44isoforms, thereby controlling the distribution of lesions in the CNS. The interference with this mechanism(s) represents a potential tool for prevention and treatment of autoimmune relapses and exacerbations.Graphical abstractDisplay OmittedHighlights•Environment and genetic are both involved in the regulation of T cell motility•Pathogens and commensals impact on T cell trafficking through a TLRs/CD44v axis•Regulation of CD44 isoforms by TLRs is a new pathogenetic mechanism of autoimmunity•Modulation of CD44 isoform can be a new target for therapy of multiple sclerosisMolecular biology; Immunology; Cell biology