PMID- 21933790 OWN - NLM STAT- MEDLINE DCOM- 20120112 LR - 20130520 IS - 1462-0332 (Electronic) IS - 1462-0324 (Linking) VI - 50 IP - 12 DP - 2011 Dec TI - Antigen-specific immature dendritic cell vaccine ameliorates anti-dsDNA antibody-induced renal damage in a mouse model. PG - 2187-96 LID - 10.1093/rheumatology/ker231 [doi] AB - OBJECTIVES: Dendritic cells (DCs) can inhibit immune response by clonal anergy when immature. Recent studies have shown that immature DCs (iDCs) may serve as a live cell vaccine after specific antigen pulse based on its potential of blocking antibody production. In this study, we aimed to investigate the effects of nuclear antigen-pulsed iDCs in the treatment of lupus-like renal damages induced by anti-dsDNA antibodies. METHODS: iDCs were generated from haemopoietic stem cells in bone marrow and then pulsed in vitro with nuclear antigen. The iDC vaccine and corresponding controls were injected into mice with lupus-like renal damages. The evaluation of disease was monitored by biochemical parameters and histological scores. Anti-dsDNA antibody isotypes and T-lymphocyte-produced cytokines were analysed for elucidating therapeutic mechanisms. RESULTS; The mice treated with antigen-pulsed iDCs had a sustained remission of renal damage compared with those injected with non-pulsed iDCs or other controls, including decreased anti-dsDNA antibody level, less proteinuria, lower blood urea nitrogen and serum creatinine values, and improved histological evaluation. Analysis on isotypes of anti-dsDNA antibody showed that iDC vaccine preferentially inhibited the production of IgG3, IgG2b and IgG2a. Furthermore, administration of antigen-treated iDCs to mice resulted in significantly reduced IL-2, IL-4 and IL-12 and IFN-gamma produced by T-memory cells. Conversely, the vaccination of antigen-pulsed mature DCs led to increased anti-dsDNA antibody production and an aggravation of lupus-like disease in the model. CONCLUSIONS; These results suggested the high potency of iDC vaccine in preventing lupus-like renal injuries induced by pathogenic autoantibodies. FAU - Xia, Yumin AU - Xia Y AD - Department of Dermatology, Renmin Hospital of Wuhan University, Wuhan, China. ymxia@whu.edu.cn FAU - Jiang, Shan AU - Jiang S FAU - Weng, Shenhong AU - Weng S FAU - Lv, Xiaochun AU - Lv X FAU - Cheng, Hong AU - Cheng H FAU - Fang, Chunhong AU - Fang C LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110920 PL - England TA - Rheumatology (Oxford) JT - Rheumatology (Oxford, England) JID - 100883501 RN - 0 (Antibodies, Antinuclear) RN - 0 (Cytokines) RN - 0 (DNA, Protozoan) RN - 0 (Vaccines, DNA) SB - IM MH - Analysis of Variance MH - Animals MH - Antibodies, Antinuclear/*immunology MH - Cytokines/biosynthesis MH - DNA, Protozoan/*administration & dosage/immunology MH - Dendritic Cells/*immunology MH - Female MH - Immunophenotyping MH - Kidney Diseases/immunology/pathology/*prevention & control MH - Lupus Erythematosus, Systemic/immunology/pathology/*prevention & control MH - Mice MH - Mice, Inbred BALB C MH - Proteinuria/etiology MH - Rats MH - Rats, Wistar MH - T-Lymphocytes/metabolism MH - Trypanosoma/immunology MH - Vaccines, DNA/*administration & dosage EDAT- 2011/09/22 06:00 MHDA- 2012/01/13 06:00 CRDT- 2011/09/22 06:00 PHST- 2011/09/22 06:00 [entrez] PHST- 2011/09/22 06:00 [pubmed] PHST- 2012/01/13 06:00 [medline] AID - ker231 [pii] AID - 10.1093/rheumatology/ker231 [doi] PST - ppublish SO - Rheumatology (Oxford). 2011 Dec;50(12):2187-96. doi: 10.1093/rheumatology/ker231. Epub 2011 Sep 20.