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J Immunol. 2014 Jun 15;192(12):5679-86. doi: 10.4049/jimmunol.1302755. Epub 2014 May 7.

Deletion of CD24 impairs development of heat shock protein gp96-driven autoimmune disease through expansion of myeloid-derived suppressor cells.

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Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425; and.
Center for Cancer and Immunology Research, Children's National Medical Center, Washington, DC 20010.
Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425; and


CD24 binds to and suppresses inflammation triggered by danger-associated molecular patterns such as heat shock proteins (HSPs) and high-mobility group box 1. Paradoxically, CD24 has been shown to enhance autoimmune disease. In this study, we attempt to reconcile this paradox by deletion of CD24 (24KO) in a lupus-like disease model driven by forced expression of HSP gp96 at the cell surface (transgenic mice [tm]). As expected, tm24KO mice showed increased CD11c(+) dendritic cell activation coupled to a significant increase in dendritic cell-specific IL-12 production compared with tm mice. However, tm24KO mice showed less CD4 T cell activation and peripheral inflammatory cytokine production in comparison with tm mice. We characterized an enhanced immune suppressive milieu in tm24KO mice distinguished by increased TGF-β and greater regulatory T cell-suppressive capacity. We found greater absolute numbers of myeloid-derived suppressor cells (MDSCs) in tm24KO mice and showed that the Ly6C(+) MDSC subset had greater suppressive capacity from tm24KO mice. Deletion of CD24 in tm mice led to diminished lupus-like pathology as evidenced by anti-nuclear Ab deposition and glomerulonephritis. Finally, we show that expanded MDSC populations were mediated by increased free high-mobility group box 1 in tm24KO mice. Thus, the deletion of CD24 in an HSP-driven model of autoimmunity led to the unexpected development of regulatory T cell and MDSC populations that augmented immune tolerance. Further study of these populations as possible negative regulators of inflammation in the context of autoimmunity is warranted.

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