PMID- 29456655 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20201001 IS - 1792-0981 (Print) IS - 1792-1015 (Electronic) IS - 1792-0981 (Linking) VI - 15 IP - 3 DP - 2018 Mar TI - Effect of immune tolerance induced by immature dendritic cells and CTLA4-Ig on systemic lupus erythematosus: An in vivo study. PG - 2499-2506 LID - 10.3892/etm.2018.5697 [doi] AB - Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disease in which tissue damage is caused by autoantibodies. The induction of specific immune tolerance, including the utilization of immune regulatory cells, may enhance the therapeutic effects of organ transplantation in patients with SLE. Furthermore, inhibiting immune responses has been reported to be an effective treatment for SLE. However, few studies have explored the association between an increased immune tolerance and a decreased immune response in SLE treatment. Dendritic cells (DCs), which are highly efficient antigen-presenting cells, are able to induce specific tolerance, while cytotoxic T lymphocyte antigen 4-immunoglobulin (CTLA4-Ig) inhibits the immune response. In the present study, interleukin (IL)-10-treated DCs and CTLA4-Ig were administered to mice with SLE alone or in combination and the therapeutic effects were investigated. IL-10 was added into the culture medium of bone marrow-derived DCs to prevent them from differentiating into mature cells. Low levels of major histocompatibility complex II, cluster of differentiation (CD)40, CD80 and CD86 were detected, which indicated that the immature state of DCs was maintained. IL-10-treated DCs were subsequently injected into the caudal vein of B6.MRL-Fas(lpr)/J lupus mice, which are an established animal model of SLE. To amplify the tolerance effect, mice were simultaneously injected with CTLA4-Ig. Compared with the IL-10-treated DC and CTLA4-Ig groups, combined treatment with IL-10-treated DCs and CTLA4-Ig strongly induced immune tolerance in mice with SLE, as indicated by the significantly reduced levels of urine protein, anti-nuclear antibody, double-stranded DNA and IL-17A. A significant decrease in the proportion of T helper cells and an increase in the proportion of CD4(+) forkhead box protein P3(+) Treg cells was also observed, further confirming the induction of immune tolerance. These results suggest that combined treatment with IL-10-DCs and CTLA4-Ig may be a promising novel therapeutic strategy for the treatment of SLE. FAU - Huang, Cuili AU - Huang C AD - Department of Dermatology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China. FAU - Zhang, Lidan AU - Zhang L AD - Department of Dermatology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China. FAU - Ling, Fang AU - Ling F AD - Department of Cell Biology and Genetics, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China. FAU - Wen, Sijian AU - Wen S AD - Department of Dermatology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China. FAU - Luo, Yanyan AU - Luo Y AD - Department of Dermatology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China. FAU - Liu, Hui AU - Liu H AD - Department of Dermatology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China. FAU - Liu, Jingping AU - Liu J AD - Department of Dermatology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China. FAU - Zheng, Wenjun AU - Zheng W AD - Department of Dermatology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China. FAU - Liang, Ming AU - Liang M AD - Department of Dermatology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China. FAU - Sun, Jian AU - Sun J AD - Department of Cell Biology and Genetics, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China. FAU - Lin, You-Kun AU - Lin YK AD - Department of Dermatology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China. LA - eng PT - Journal Article DEP - 20180104 PL - Greece TA - Exp Ther Med JT - Experimental and therapeutic medicine JID - 101531947 PMC - PMC5795536 OTO - NOTNLM OT - cytotoxic T lymphocyte antigen 4-immunoglobulin OT - immature dendritic cells OT - interleukin-10 OT - systemic lupus erythematosus OT - tolerance EDAT- 2018/02/20 06:00 MHDA- 2018/02/20 06:01 PMCR- 2018/01/04 CRDT- 2018/02/20 06:00 PHST- 2016/09/21 00:00 [received] PHST- 2017/07/27 00:00 [accepted] PHST- 2018/02/20 06:00 [entrez] PHST- 2018/02/20 06:00 [pubmed] PHST- 2018/02/20 06:01 [medline] PHST- 2018/01/04 00:00 [pmc-release] AID - ETM-0-0-5697 [pii] AID - 10.3892/etm.2018.5697 [doi] PST - ppublish SO - Exp Ther Med. 2018 Mar;15(3):2499-2506. doi: 10.3892/etm.2018.5697. Epub 2018 Jan 4.