{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T03:51:29Z","timestamp":1761709889334,"version":"3.41.2"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,8,26]],"date-time":"2021-08-26T00:00:00Z","timestamp":1629936000000},"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:p>Myeloid-derived suppressor cells (MDSCs) emerge as a promising candidate for the immunotherapy of autoimmune hepatitis (AIH). However, targets for modulating MDSC in AIH are still being searched. Liver X receptors (LXRs) are important nuclear receptors linking lipid metabolism and immune responses. Despite the extensive studies of LXR in myeloid compartment, its role in MDSCs is currently less understood. Herein, expression of LXR\u03b1 was found to be upregulated in AIH patients and colocalized with hepatic MDSCs. In ConA-induced hepatitis, deletion of LXR\u03b1 led to increased expansion of MDSCs in the liver and alleviated the hepatic injury. MDSCs in LXR\u03b1<jats:sup>\u2212\/\u2212<\/jats:sup> mice exhibited enhanced proliferation and survival comparing with WT mice. T-cell proliferation assay and adoptive cell transfer experiment validated the potent immunoregulatory role of MDSCs <jats:italic>in\u00a0vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>. Mechanistically, MDSCs from LXR\u03b1<jats:sup>\u2212\/\u2212<\/jats:sup> mice possessed significantly lower expression of interferon regulatory factor 8 (IRF-8), a key negative regulator of MDSC differentiation. Transcriptional activation of IRF-8 by LXR\u03b1 was further demonstrated<\/jats:p><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We reported that abrogation of LXR\u03b1 facilitated the expansion of MDSCs <jats:italic>via<\/jats:italic> downregulating IRF-8, and thereby ameliorated hepatic immune injury profoundly. Our work highlights the therapeutic potential of targeting LXR\u03b1 in AIH.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2021.732102","type":"journal-article","created":{"date-parts":[[2021,8,26]],"date-time":"2021-08-26T09:21:17Z","timestamp":1629969677000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Myeloid-Derived Suppressive Cells Deficient in Liver X Receptor \u03b1 Protected From Autoimmune 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