{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T07:39:45Z","timestamp":1790840385002,"version":"4.1.0"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,6,3]],"date-time":"2022-06-03T00:00:00Z","timestamp":1654214400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001409","name":"Department of Science and Technology, Ministry of Science and Technology, India","doi-asserted-by":"publisher","award":["SB\/EF\/02\/2016"],"award-info":[{"award-number":["SB\/EF\/02\/2016"]}],"id":[{"id":"10.13039\/501100001409","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"\n Background<\/jats:title>\n Decompensated cirrhosis patients are more prone to bacterial infections. Myeloid-derived suppressor cells (MDSCs) expand in sepsis patients and disrupt immune cell functions. Granulocyte-macrophage colony-stimulating factor (GM-CSF) therapy helps in restoring immune cell functions and resolving infections. Its role in MDSC modulation in cirrhosis with sepsis is not well understood.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n A total of 164 decompensated cirrhotic\u201462 without (w\/o), 72 with sepsis, and 30 with sepsis treated with GM-CSF\u2014and 15 healthy were studied. High-dimensional flow cytometry was performed to analyze MDSCs, monocytes, neutrophils, CD4 T cells, and Tregs at admission and on days 3 and day 7.\n Ex vivo<\/jats:italic>\n co-cultured MDSCs with T cells were assessed for proliferation and apoptosis of T cells and differentiation to Tregs. Plasma factors and mRNA levels were analyzed by cytokine-bead assay and qRT-PCR.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Frequencies of MDSCs and Tregs were significantly increased (\n p<\/jats:italic>\n = 0.011 and\n p<\/jats:italic>\n = 0.02) with decreased CD4 T cells (\n p<\/jats:italic>\n = 0.01) in sepsis than w\/o sepsis and healthy controls (HCs) (\n p<\/jats:italic>\n = 0.000,\n p<\/jats:italic>\n = 0.07, and\n p<\/jats:italic>\n = 0.01) at day 0 and day 7. In sepsis patients, MDSCs had increased IL-10, Arg1, and iNOS mRNA levels (\n p<\/jats:italic>\n = 0.016,\n p<\/jats:italic>\n = 0.043, and\n p<\/jats:italic>\n = 0.045).\n Ex vivo<\/jats:italic>\n co-cultured MDSCs with T cells drove T-cell apoptosis (\n p<\/jats:italic>\n = 0.03,\n p<\/jats:italic>\n = 0.03) with decreased T-cell proliferation and enhanced FOXP3\n +<\/jats:sup>\n expression (\n p<\/jats:italic>\n = 0.044 and\n p<\/jats:italic>\n = 0.043) in sepsis compared to w\/o sepsis at day 0. Moreover, blocking the MDSCs with inhibitors suppressed FOXP3 expression. GM-CSF treatment in sepsis patients significantly decreased MDSCs and FOXP3\n +<\/jats:sup>\n Tregs but increased CD4 T-cell functionality and improved survival.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n MDSCs have an immunosuppressive function by expanding FOXP3\n +<\/jats:sup>\n Tregs and inhibiting CD4\n +<\/jats:sup>\n T-cell proliferation in sepsis. GM-CSF treatment suppressed MDSCs, improved T-cell functionality, and reduced Tregs in circulation.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fimmu.2022.828949","type":"journal-article","created":{"date-parts":[[2022,6,3]],"date-time":"2022-06-03T08:49:29Z","timestamp":1654246169000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":25,"title":["Granulocyte-Macrophage Colony-Stimulating Factor Modulates Myeloid-Derived Suppressor Cells and Treg Activity in Decompensated Cirrhotic Patients With Sepsis"],"prefix":"10.3389","volume":"13","author":[{"given":"Rashi","family":"Sehgal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rakhi","family":"Maiwall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijayaraghavan","family":"Rajan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mojahidul","family":"Islam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sukriti","family":"Baweja","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Navkiran","family":"Kaur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guresh","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gayatri","family":"Ramakrishna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiv K.","family":"Sarin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nirupma","family":"Trehanpati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,6,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.30412","article-title":"Management of Sepsis in Patients With Cirrhosis: Current Evidence and Practical Approach","volume":"70","author":"Simonetto","year":"2019","journal-title":"Hepatology"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23264","article-title":"Severe Sepsis in Cirrhosis","volume":"50","author":"Gustot","year":"2009","journal-title":"Hepatology"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1002\/hep.28906","article-title":"Portal Hypertensive Bleeding in Cirrhosis: Risk Stratification, Diagnosis, and Management: 2016 Practice Guidance by the American Association 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