{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T21:13:05Z","timestamp":1769548385267,"version":"3.49.0"},"reference-count":60,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T00:00:00Z","timestamp":1738627200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Obesity is associated with dysregulated metabolism and low-grade chronic inflammation in adipose tissue (AT). Immune cells, including macrophages, T cells, and neutrophils, infiltrate the AT and secrete proinflammatory cytokines to exacerbate the AT inflammation. RNA-Seq analysis of AT immune cells isolated from mice fed a high-fat diet (HFD) versus normal fat diet (ND) identified a panel of genes that were markedly downregulated, including sialic acid-binding Ig-like lectin E (siglec-E), in HFD compared to ND mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A series of experiments in wild-type (WT) and siglec-E knockout (siglec-E KO) mice was designed to investigate the effect of HFD on the functional role of siglec-E in the regulation of AT inflammation and adipogenesis. We analyzed the changes in immune phenotypes, inflammatory response, adipogenesis, and levels of cytokines and chemokines after HFD and ND feeding.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>HFD consumption significantly increased the body weight and blood glucose levels in siglec-E KO mice relative to those of WT mice. This was associated with an increased infiltration of macrophages, CXCR3 expressing CD8 T cells, and monocytic myeloid-derived suppressor cells (M-MDSCs) with a concomitant decrease in numbers of dendritic cells (DCs), in the AT of siglec-E KO fed HFD versus the WT HFD counterparts. The HFD-fed siglec-E KO mice also exhibited elevated expression of intracellular Akt and TNF receptor-associated factor 3 (TRAF3) signaling, inducing C\/EBP\u03b1, FASN, PPAR\u03b3, and resistin in suprascapular AT compared to WT HFD-fed mice. Taken together, these results suggest that a genetic deficiency of siglec-E plays a key role in inducing AT inflammation by differentially altering M-MDSCs and CD8<jats:sup>+<\/jats:sup>CXCR3<jats:sup>+<\/jats:sup> T cell function and adipogenesis by TRAF3 and Akt signaling in AT.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings strongly suggest that modulation of siglec-E pathways might have a protective effect at least in part against AT inflammation and metabolic disorders.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1501307","type":"journal-article","created":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T06:32:50Z","timestamp":1738650770000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Siglec-E augments adipose tissue inflammation by modulating TRAF3 signaling and monocytic myeloid-derived suppressor cells during 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