{"title":"From Bench to Bedside: Reframing the <i>CXCL13</i>/<i>CXCR5</i> Axis as a Non-Redundant Organizer of Protective Pulmonary Immunity in COVID-19.","authors":"Lbachir BenMohamed","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":520327,"journal":{"name":"Journal of clinical & cellular immunology","volume":"17 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13521606/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148842155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Isatou Bah, Dima Youssef, Mary E Howell, Zhi Q Yao, Charles E McCall, Mohamed El Gazzar
{"title":"Nuclear <i>S100A9</i> Protein Induces Anti-Inflammatory Gene Expression in Sepsis.","authors":"Isatou Bah, Dima Youssef, Mary E Howell, Zhi Q Yao, Charles E McCall, Mohamed El Gazzar","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Expansion and accumulation of Myeloid-Derived Suppressor Cells (MDSCs) during sepsis contribute to post-sepsis immunosuppression, as these cells suppress innate and adaptive immunity. We have shown that the proinflammatory <i>S100A9</i> protein accumulates in the nucleus of MDSCs during late sepsis in both mice and humans. In this context, nuclear <i>S100A9</i> acts as a transcription co-factor to induce the expression of two potent immunosuppressive cytokines, Interleukin-10 (IL-10) and Transforming Growth Factor-β (TGF-β). <i>S100A9</i> knockdown in MDSCs from late septic mice and late septic patients significantly reduced IL-10 and TGF-β production upon <i>ex vivo</i> stimulation with bacterial lipopolysaccharide. In contrast, ectopic expression of <i>S100A9</i> in MDSCs from <i>S100A9</i>-deficient mice significantly increased IL-10 and TGF-β production. Chromatin immunoprecipitation revealed that <i>S100A9</i> protein binds at the IL-10 and TGF-β promoters. Moreover, co-transfection of <i>S100A9</i> expression plasmid with a luciferase reporter gene under the control of IL-10 or TGF-β promoter induced the luciferase gene expression in MDSCs from <i>S100A9</i>-deficient mice. Notably, in vivo depletion of long noncoding Ribonucleic Acid (RNA) <i>Hotairm1</i>, which induces <i>S100A9</i> protein accumulation in MDSCs during late sepsis, reduced IL-10 and TGF-β production <i>ex vivo</i>. Since IL-10 and TGF-β enhance sepsis immunosuppression and are associated with worse outcomes, our findings suggest that targeting <i>S100A9</i> may mitigate the immunosuppressive effects of MDSCs in late sepsis.</p>","PeriodicalId":520327,"journal":{"name":"Journal of clinical & cellular immunology","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12129438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144210631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Isatou Bah, Dima Youssef, Zhi Q Yao, Charles E McCall, Mohamed El Gazzar
{"title":"Hotairm1 Controls S100A9 Protein Phosphorylation in Myeloid-Derived Suppressor Cells during Sepsis.","authors":"Isatou Bah, Dima Youssef, Zhi Q Yao, Charles E McCall, Mohamed El Gazzar","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>During the acute phase of sepsis, the S100A9 proinflammatory protein resides in the cytosol in a phosphorylated form. In contrast, S100A9 relocalizes to the nucleus in an unphosphorylated form during the late/chronic sepsis state of immunometabolic paralysis. We reported that Hotairm1, a long noncoding RNA, facilitates S100A9 nuclear location in myeloid-derived suppressor cells. Here, we show that Hotairm1 promotes S100A9 nuclear location by limiting its phosphorylation by p38 MAPK. Knockdown of Hotairm1 in MDSCs from mice and humans with late sepsis increases phospho-S100A9 protein. Conversely, increasing Hotairm1 in early sepsis Gr1<sup>+</sup>CD11b<sup>+</sup> cells by transfection decreases phospho-S100A9 protein levels. Notably, increasing S100A9 protein phosphorylation in late sepsis MDSCs <i>via</i> Hotairm1 knockdown decreases the production of the immunosuppressive cytokine IL-10. These results suggest that targeting Hotairm1 might reduce MDSC expansion during sepsis and thus relieve immunosuppression and improve survival.</p>","PeriodicalId":520327,"journal":{"name":"Journal of clinical & cellular immunology","volume":"14 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11633817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142815325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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