A Camelid-Derived STAT-Specific Nanobody Inhibits Neuroinflammation and Ameliorates Experimental Autoimmune Encephalomyelitis (EAE)

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dc.contributor.authorMbanefo, Evaristus C.en
dc.contributor.authorSeifert, Allisonen
dc.contributor.authorYadav, Manoj Kumaren
dc.contributor.authorYu, Cheng-Rongen
dc.contributor.authorNagarajan, Vijayarajen
dc.contributor.authorParihar, Ashutoshen
dc.contributor.authorSingh, Sunandaen
dc.contributor.authorEgwuagu, Charles E.en
dc.date.accessioned2024-06-26T13:34:09Zen
dc.date.available2024-06-26T13:34:09Zen
dc.date.issued2024-06-16en
dc.date.updated2024-06-26T13:23:08Zen
dc.description.abstractProinflammatory T-lymphocytes recruited into the brain and spinal cord mediate multiple sclerosis (MS) and currently there is no cure for MS. IFN-γ-producing Th1 cells induce ascending paralysis in the spinal cord while IL-17-producing Th17 cells mediate cerebellar ataxia. STAT1 and STAT3 are required for Th1 and Th17 development, respectively, and the simultaneous targeting of STAT1 and STAT3 pathways is therefore a potential therapeutic strategy for suppressing disease in the spinal cord and brain. However, the pharmacological targeting of STAT1 and STAT3 presents significant challenges because of their intracellular localization. We have developed a STAT-specific single-domain nanobody (SBT-100) derived from camelids that targets conserved residues in Src homolog 2 (SH2) domains of STAT1 and STAT3. This study investigated whether SBT-100 could suppress experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. We show that SBT-100 ameliorates encephalomyelitis through suppressing the expansion of Th17 and Th1 cells in the brain and spinal cord. Adoptive transfer experiments revealed that lymphocytes from SBT-100-treated EAE mice have reduced capacity to induce EAE, indicating that the immunosuppressive effects derived from the direct suppression of encephalitogenic T-cells. The small size of SBT-100 makes this STAT-specific nanobody a promising immunotherapy for CNS autoimmune diseases, including multiple sclerosis.en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationMbanefo, E.C.; Seifert, A.; Yadav, M.K.; Yu, C.-R.; Nagarajan, V.; Parihar, A.; Singh, S.; Egwuagu, C.E. A Camelid-Derived STAT-Specific Nanobody Inhibits Neuroinflammation and Ameliorates Experimental Autoimmune Encephalomyelitis (EAE). Cells 2024, 13, 1042.en
dc.identifier.doihttps://doi.org/10.3390/cells13121042en
dc.identifier.urihttps://hdl.handle.net/10919/119517en
dc.language.isoenen
dc.publisherMDPIen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectnanobodyen
dc.subjectSBT-100en
dc.subjectencephalomyelitisen
dc.subjectEAEen
dc.subjectautoimmunityen
dc.subjectSTAT1en
dc.subjectSTAT3en
dc.subjectSH2 domainen
dc.subjectTh17en
dc.subjectTh1en
dc.titleA Camelid-Derived STAT-Specific Nanobody Inhibits Neuroinflammation and Ameliorates Experimental Autoimmune Encephalomyelitis (EAE)en
dc.title.serialCellsen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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