Distinct role of FoxO1 in M‐CSF‐ and GM‐CSF‐differentiated macrophages contributes LPS‐mediated IL‐10: implication in hyperglycemia

[摘要] Macrophagesareaheterogeneouspopulationofimmunecellsthatareessentialfortheinitiationandcontainmentinflammation.Thereare2well‐establishedpopulationsofinflammatorymacrophages:classicallyactivatedM1andalternativelyactivatedM2macrophages.TheFoxOfamilyoftranscriptionfactorsplayskeyrolesinanumberofcellularprocesses,includingcellgrowth,metabolism,survival,andinflammation.Inthisstudy,wedeterminedwhethertheexpressionofFoxO1contributespolarizationofmacrophagestowardtheM2‐likephenotypebyenhancingIL‐10cytokineexpression.WeidentifiedthatFoxO1ishighlyexpressedinM‐CSF‐derived(M2‐like)macrophagesubsets,andthisM2‐likemacrophagesshowedapreferentialFoxO1enrichmentontheIL‐10promoterbutnotinGM‐CSF‐derived(M1‐like)macrophagesduringclassicactivationbyLPStreatment,whichsuggeststhatFoxO1enhancesIL‐10bybindingdirectlytotheIL‐10promoter,especiallyinBMMs.Inaddition,ourdatashowthatmacrophagesinthesettingofhyperglycemiacontributetothemacrophage‐inflammatoryphenotypethroughattenuationofthecontributionofFoxO1toactivateIL‐10expression.OurdataidentifyanovelroleforFoxO1inregulatingIL‐10secretionduringclassicactivationandhighlightthepotentialfortherapeuticinterventionsforchronicinflammatoryconditions,suchasatherosclerosis,diabetes,inflammatoryboweldisease,andarthritis...

[学科分类] 生理学

[关键词] monocyte;metabolic stress;M1‐like;M2‐like;inflammation