title: A novel epitope from CD22 regulates Th1 and Th17 cell function in systemic lupus erythematosus.
abstract: The published antibodies (Abs) against CD22 on B cells including Epratuzumab could inhibit B cell activation mainly through binding to C2-set Ig domain of CD22, but they are rarely reported to modulate the pathogenic CD4(+) T cell function in systemic lupus erythematosus (SLE). Recently, it was proved that the extracellular amino-terminal V-set Ig domain of CD22 might mediate the interaction of B and T cells, but for now the exact effect of this domain on CD4(+) T cell biology have not been identified. Thus, in this study, we screened out a peptide termed B2285 from this V-set Ig domain, developed the novel specific anti-B2285 Abs in rabbits, and investigated their effects in MRL/lpr mice with spontaneous SLE. The results showed that anti-B2285 Abs could ameliorate the disease severity obviously in spontaneous SLE mice with the decreased differentiations of Th1 and Th17 cells and no changes of Th2 and Treg cells. In co-cultured B cells and CD4(+) T cells, this specific anti-CD22 Abs was observed to inhibit the anti-dsDNA Abs production, CD4(+) T cells proliferation, the protein levels of T-bet and RORγt, and the mRNA levels of TNF-α, IFN-γ, IL-6 and IL-17 in CD4(+) T cells. Moreover, the expression of CD45RO on CD4(+) T cells could be also apparently diminished by this novel Abs. The data suggested that anti-B2285 Abs could slow SLE progression significantly by regulating Th1 and Th17 cells function via B-T cell interaction and the cytokine network regulation. The treatment against V-set Ig domain of CD22 would be a valuable therapeutic method for SLE and other autoimmune diseases.
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yuan
authors.forename: Miao
authors.initials: M
authors.lastname: Yu
authors.forename: Ai-Lin
authors.initials: AL
authors.lastname: Cao
authors.forename: Xiao
authors.initials: X
authors.lastname: Chen
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Zhang
authors.forename: You
authors.initials: Y
authors.lastname: Song
authors.forename: Xiang
authors.initials: X
authors.lastname: Cheng
authors.forename: Zi-Hua
authors.initials: ZH
authors.lastname: Zhou
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.forename: He-Ping
authors.initials: HP
authors.lastname: Guo
authors.forename: Rong
authors.initials: R
authors.lastname: Du
authors.forename: Yu-Hua
authors.initials: YH
authors.lastname: Liao
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D000918:Antibody Specificity / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D002450:Cell Communication; D002454:Cell Differentiation / Q000276:immunology; D002469:Cell Separation; D000939:Epitopes / Q000276:immunology*; D005260:Female; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000473:pathology; D051379:Mice; D019463:Mice, Inbred MRL lpr; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D017434:Protein Structure, Tertiary; D011817:Rabbits; D012720:Severity of Illness Index; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000737:chemistry / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology* / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology* / Q000473:pathology
chemical_list: D000906:Antibodies; D000939:Epitopes; D010455:Peptides; D051918:Sialic Acid Binding Ig-like Lectin 2