PMID- 30053444 OWN - NLM STAT- MEDLINE DCOM- 20190930 LR - 20190930 IS - 1090-2422 (Electronic) IS - 0014-4827 (Linking) VI - 370 IP - 2 DP - 2018 Sep 15 TI - The suppression effect of dendritic cells maturation by adipose-derived stem cells through TGF-beta1 related pathway. PG - 708-717 LID - S0014-4827(18)30569-X [pii] LID - 10.1016/j.yexcr.2018.07.037 [doi] AB - BACKGROUND: Our previous studies demonstrated that adipose-derived stem cells (ASCs) could modulate regulatory T cells (Treg) and prolong hind-limb allotransplant survival in vitro and in vivo. Dendritic cells (DCs) play a pivotal role in innate and adaptive immunity. The aim of this study is to investigate the underlying mechanism of ASCs in modulating DC maturation. MATERIALS AND METHODS: ASCs were isolated from rodent adipose tissue, DCs were derived from the bone marrow, and CD4(+) T cells were purified from splenocytes. DCs were co-cultured with ASCs to evaluate the suppressive effects of ASCs. CD4(+) T-cells were co-cultured with DCs pre-treated with or without ASCs. The cell surface markers of DCs were analyzed by flow cytometry. T-cell proliferation was analyzed by the BrdU proliferation test. Tolerogenic cytokines and indoleamine 2,3-dioxygenase (IDO) expressions after different treatments were detected by quantitative real-time PCR, Western blotting, and ELISA analysis. RESULT: ASCs suppressed DC maturation as evidenced by low expressions of CD80, CD86, and MHC-II. Also, ASC-treated mature DCs showed higher levels of TGF-beta1, IL-10, and IDO expressions, as compared to that in matured DCs (mDCs) alone. ASC-treated mDCs co-cultured with CD4(+) T cells revealed a significant higher percentage of Treg than mDC without treatment. The IDO level in ASC-treated mDCs and Treg induction effects were blocked by the ASCs pre-treated with TGF-beta1 siRNAs, but not IL-10 siRNAs. CONCLUSION: ASC-modulated DC maturation correlated with TGF-beta1 secretion, IDO expression, and Treg induction. ASCs could be used as a potential immunomodulatory strategy for clinical application in allotransplantation. CI - Copyright (c) 2018 Elsevier Inc. All rights reserved. FAU - Wang, Yu-Chi AU - Wang YC AD - Division of Plastic Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. FAU - Chen, Rong-Fu AU - Chen RF AD - Division of Plastic Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. FAU - Brandacher, Gerald AU - Brandacher G AD - Department of Plastic and Reconstructive Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, United States. FAU - Lee, W P Andrew AU - Lee WPA AD - Department of Plastic and Reconstructive Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, United States. FAU - Kuo, Yur-Ren AU - Kuo YR AD - Division of Plastic Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Faculty of Medicine, College of Medicine, Orthopaedic Research Center and Stem Cell Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan. Electronic address: t1207816@ms22.hinet.net. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180724 PL - United States TA - Exp Cell Res JT - Experimental cell research JID - 0373226 RN - 0 (Cytokines) RN - 0 (Transforming Growth Factor beta1) SB - IM MH - Adipocytes/*cytology MH - Adipose Tissue/cytology MH - Animals MH - Cell Differentiation/physiology MH - Cell Proliferation/physiology MH - Cells, Cultured MH - Cytokines/metabolism MH - Dendritic Cells/*immunology MH - Lymphocyte Activation/immunology MH - Male MH - Mesenchymal Stem Cells/*cytology MH - Rats MH - T-Lymphocytes, Regulatory/immunology MH - Transforming Growth Factor beta1/*metabolism OTO - NOTNLM OT - Adipose-derived stem cells OT - Dendritic cells OT - Indoleamine 2,3-dioxygenase OT - Transforming growth factor beta1 EDAT- 2018/07/28 06:00 MHDA- 2019/10/01 06:00 CRDT- 2018/07/28 06:00 PHST- 2018/02/23 00:00 [received] PHST- 2018/07/22 00:00 [revised] PHST- 2018/07/23 00:00 [accepted] PHST- 2018/07/28 06:00 [pubmed] PHST- 2019/10/01 06:00 [medline] PHST- 2018/07/28 06:00 [entrez] AID - S0014-4827(18)30569-X [pii] AID - 10.1016/j.yexcr.2018.07.037 [doi] PST - ppublish SO - Exp Cell Res. 2018 Sep 15;370(2):708-717. doi: 10.1016/j.yexcr.2018.07.037. Epub 2018 Jul 24.