{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T17:14:36Z","timestamp":1791566076423,"version":"4.3.4"},"reference-count":59,"publisher":"American Society for Clinical Investigation","issue":"15","license":[{"start":{"date-parts":[[2024,8,1]],"date-time":"2024-08-01T00:00:00Z","timestamp":1722470400000},"content-version":"vor","delay-in-days":51,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH\/NINDS","award":["R01 NS107851"],"award-info":[{"award-number":["R01 NS107851"]}]},{"name":"GBS\/CIDP Foundation International","award":["-"],"award-info":[{"award-number":["-"]}]},{"name":"U.S. Department of Defense","award":["Medical Research W81XWH2110918"],"award-info":[{"award-number":["Medical Research W81XWH2110918"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,8,1]]},"abstract":"<jats:p>\n                    Inflammatory neuropathies, which include chronic inflammatory demyelinating polyneuropathy (CIDP) and Guillain Barr\u00e9 syndrome (GBS), result from autoimmune destruction of the PNS and are characterized by progressive weakness and sensory loss. CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells play a key role in the autoimmune destruction of the PNS. Yet, key properties of pathogenic CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells remain incompletely understood. Here, we used paired single-cell RNA-Seq (scRNA-Seq) and single-cell T cell receptor\u2013sequencing (scTCR-Seq) of peripheral nerves from an inflammatory neuropathy mouse model to identify IL-21\u2013expressing CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells that were clonally expanded and multifunctional. These IL-21\u2013expressing CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells consisted of 2 transcriptionally distinct expanded cell populations, which expressed genes associated with T follicular helper (Tfh) and T peripheral helper (Tph) cell subsets. Remarkably, TCR clonotypes were shared between these 2 IL-21\u2013expressing cell populations, suggesting a common lineage differentiation pathway. Finally, we demonstrated that IL-21 receptor\u2013KO (IL-21R\u2013KO) mice were protected from neuropathy development and had decreased immune infiltration into peripheral nerves. IL-21 signaling upregulated CXCR6, a chemokine receptor that promotes CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell localization in peripheral nerves. Together, these findings point to IL-21 signaling, Tfh\/Tph differentiation, and CXCR6-mediated cellular localization as potential therapeutic targets in inflammatory neuropathies.\n                  <\/jats:p>","DOI":"10.1172\/jci178602","type":"journal-article","created":{"date-parts":[[2024,7,31]],"date-time":"2024-07-31T14:05:16Z","timestamp":1722434716000},"source":"Crossref","is-referenced-by-count":15,"title":["A pathologically expanded, clonal lineage of IL-21\u2013producing CD4+ T cells drives inflammatory neuropathy"],"prefix":"10.1172","volume":"134","author":[{"given":"Maryamsadat","family":"Seyedsadr","sequence":"first","affiliation":[{"name":"Department of Microbiology, Immunology, and Molecular Genetics and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madison F.","family":"Bang","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Molecular Genetics 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