{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T04:51:19Z","timestamp":1782449479844,"version":"3.54.5"},"reference-count":94,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T00:00:00Z","timestamp":1782432000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Ulcerative colitis (UC) is an intestinal immune disorder of unknown etiology. Mounting evidence reveals a central role of macrophages in the hemostatic balance of gut immunity, and dysfunctional macrophages are associated with UC pathogenesis. Granulocyte macrophage-colony stimulating factor (GM-CSF) is an essential modulator of macrophages and has recently been recognized as a potential target in many autoimmune disorders. However, the action of GM-CSF in gut inflammation remains unspecified.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The significance of GM-CSF in UC and its mechanism of action were investigated. GM-CSF expression was examined in colon biopsy tissues from UC patients and healthy controls. A dextran sodium sulfate (DSS)-induced colitis mouse model was used to evaluate the effect of GM-CSF neutralizing antibody (GM-CSF Ab). Macrophage infiltration, CD4+ T helper (Th) cell responses, macrophage polarization, and glycolysis-related genes were assessed using in vivo and in vitro experiments. The involvement of the Akt\/mTOR pathway was also examined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>GM-CSF expression was significantly elevated in colon biopsy tissues from UC patients compared to controls. Administration of GM-CSF Ab to DSS-treated mice attenuated gut inflammation. Furthermore, GM-CSF Ab inhibited the infiltration of macrophages and inflammatory CD4+ Th cells into the intestine of DSS-colitis mice. In vitro experiments showed that GM-CSF induced M1-type polarization of peritoneal macrophages and subsequently augmented the Th17 response. Further experiments indicated that the proinflammatory phenotype of macrophages induced by GM-CSF was related to glycolytic metabolism, which was influenced by the Akt\/mTOR pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Collectively, this study suggests that GM-CSF is associated with the regulation of glycolytic metabolism involving the Akt\/mTOR pathway, and subsequently alters macrophage function to promote intestinal inflammation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1799536","type":"journal-article","created":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T04:38:52Z","timestamp":1782448732000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["GM-CSF promotes pro-inflammatory macrophage activation associated with Akt\/mTOR signaling during experimental 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