{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T06:42:59Z","timestamp":1775889779393,"version":"3.50.1"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,9,8]],"date-time":"2023-09-08T00:00:00Z","timestamp":1694131200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009560","name":"American Gastroenterological Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009560","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014907","name":"Gastric Cancer Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014907","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000090","name":"Congressionally Directed Medical Research Programs","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000090","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Gastric myeloid-derived suppressor cells (MDSCs) are a prominent population that expands during gastric pre-neoplastic and neoplastic development in humans and mice. However, the heterogeneity of this population has circumvented the ability to study these cells or understand their functions. Aside from Schlafen-4<jats:sup>+<\/jats:sup> (Slfn-4<jats:sup>+<\/jats:sup>) MDSCs in mouse studies, which constitute a subset of this population, limitations exist in characterizing the heterogeneity of the gastric CD11b<jats:sup>+<\/jats:sup>Ly6G<jats:sup>+<\/jats:sup> population and targeting its different subsets. Here we identify S100a8 as a pan-specific marker for this population and utilize it to study the role of the S100a8<jats:sup>+<\/jats:sup>Cxcr2<jats:sup>+<\/jats:sup> subset.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We profiled gastric CD11b<jats:sup>+<\/jats:sup>Ly6G<jats:sup>+<\/jats:sup> versus CD11b<jats:sup>+<\/jats:sup>Ly6G<jats:sup>-<\/jats:sup> myeloid cells by transcriptomic and single-cell RNA sequencing. We identified S100a8 as a pan-specific marker of the gastric granulocytic MDSC (G-MDSC) population, and generated S100a8<jats:sup>Cre<\/jats:sup>Cxcr2<jats:sup>flox\/flox<\/jats:sup> to study the effects of Cxcr2 knockdown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Following 6-months of <jats:italic>Helicobacter felis<\/jats:italic> infection, gastric CD11b<jats:sup>+<\/jats:sup>Ly6G<jats:sup>+<\/jats:sup> G-MDSCs were highly enriched for the expression of S100a8, S100a9, Slfn4, Cxcr2, Irg1, Il1f9, Hcar2, Retnlg, Wfdc21, Trem1, Csf3R, Nlrp3, and Il1b. The expression of these distinct genes following 6mo <jats:italic>H. felis<\/jats:italic> infection marked heterogeneous subpopulations, but they all represented a subset of S100a8<jats:sup>+<\/jats:sup> cells. S100a8 was identified as a pan-marker for CD11b<jats:sup>+<\/jats:sup>Ly6G<jats:sup>+<\/jats:sup> cells arising in chronic inflammation, but not neutrophils recruited during acute gut infection. 6mo <jats:italic>Helicobacter felis<\/jats:italic>-infected S100a8<jats:sup>Cre<\/jats:sup>Cxcr2<jats:sup>flox\/flox<\/jats:sup> mice exhibited worsened gastric metaplastic pathology than Cxcr2<jats:sup>flox\/flox<\/jats:sup> mice, which was associated with dysregulated lipid metabolism and peroxidation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>S100a8 is a pan-specific marker that can be used to target gastric G-MDSC subpopulations, of which the Cxcr2<jats:sup>+<\/jats:sup> subset regulates gastric immunopathology and associates with the regulation of lipid 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