Soluble CD83 Alleviates Experimental Autoimmune Uveitis by Inhibiting Filamentous Actin-Dependent Calcium Release in Dendritic Cells

Soluble CD83 (sCD83) is the extracellular domain of the membrane-bound CD83 molecule, and known for its immunoregulatory functions. Whether and how sCD83 participates in the pathogenesis of uveitis, a serious inflammatory disease of the eye that can cause visual disability and blindness, is unknown....

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Published inFrontiers in immunology Vol. 9; p. 1567
Main Authors Lin, Wei, Buscher, Konrad, Wang, Beibei, Fan, Zhichao, Song, Nannan, Li, Peng, Yue, Yingying, Li, Bingqing, Li, Cuiling, Bi, Hongsheng
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Media S.A 09.07.2018
Subjects
calcium response
dendritic cells
experimental autoimmune uveitis
filamentous actin
Immunology
soluble CD83
T cells
calcium response
dendritic cells
experimental autoimmune uveitis
T cells
filamentous actin
soluble CD83
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Summary:Soluble CD83 (sCD83) is the extracellular domain of the membrane-bound CD83 molecule, and known for its immunoregulatory functions. Whether and how sCD83 participates in the pathogenesis of uveitis, a serious inflammatory disease of the eye that can cause visual disability and blindness, is unknown. By flow cytometry and imaging studies, we show that sCD83 alleviates experimental autoimmune uveitis (EAU) through a novel mechanism. During onset and recovery of EAU, the level of sCD83 rises in the serum and aqueous humor, and CD83 leukocytes infiltrate the inflamed eye. Systemic or topical application of sCD83 exerts a protective effect by decreasing inflammatory cytokine expression, reducing ocular and splenic leukocyte including CD4 T cells and dendritic cells (DCs). Mechanistically, sCD83 induces tolerogenic DCs by decreasing the synaptic expression of co-stimulatory molecules and hampering the calcium response in DCs. These changes are caused by a disruption of the cytoskeletal rearrangements at the DC-T cell contact zone, leading to altered localization of calcium microdomains and suppressed T-cell activation. Thus, the ability of sCD83 to modulate DC-mediated inflammation in the eye could be harnessed to develop new immunosuppressive therapeutics for autoimmune uveitis.
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Specialty section: This article was submitted to Molecular Innate Immunity, a section of the journal Frontiers in Immunology
Edited by: Jinhua Lu, National University of Singapore, Singapore
These authors have contributed equally to this work.
Reviewed by: Luuk Hilbrands, Radboud University Nijmegen, Netherlands; Alexander Steinkasserer, Universitätsklinikum Erlangen, Germany
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2018.01567