PMID- 20828738 OWN - NLM STAT- MEDLINE DCOM- 20120106 LR - 20171116 IS - 1095-8673 (Electronic) IS - 0022-4804 (Linking) VI - 171 IP - 2 DP - 2011 Dec TI - Exosomes derived from immature bone marrow dendritic cells induce tolerogenicity of intestinal transplantation in rats. PG - 826-32 LID - 10.1016/j.jss.2010.05.021 [doi] AB - BACKGROUND: Dendritic cells (DCs) secrete exosomes bearing major histocompatibility complex I and II (MHC I /II) and co-stimulatory molecules, and play a critical role in immune regulation. Because immature DCs can induce T-cell tolerance in vitro and in vivo, we explored the possibility of using exosomes derived from immature DCs (imDex) for the induction of intestinal transplant tolerance in rats. MATERIALS AND METHODS: ImDex were purified from F344 rat bone marrow immature DCs. The tolerizing capacities of imDex were analyzed in vitro and in vivo using a F344-to-Wistar intestinal transplantation model. RESULTS: In the context of a moderate level of MHC class II and a low co-stimulatory level expression, imDex significantly suppressed the alloreactive T-cell response with an increase in IL-10 in vitro. In vivo injection of the lower dose (20 mug) of donor (but not recipient) imDex can significantly prolong the survival of intestinal allografts. This effect was accompanied by a decrease in the anti-donor cellular response, with a significant increase in IL-10. The CD4+CD25+T cells percentage and FOXP3mRNA expression in splenic T-cells were also significantly increased in imDex treatment recipients at five days after transplantation. CONCLUSIONS: The results suggest that imDex can prolong the intestinal allograft survival and may be a potential strategy to facilitate induction of transplant tolerance. CI - Copyright (c) 2011 Elsevier Inc. All rights reserved. FAU - Yang, Xiaojun AU - Yang X AD - Department of Gastrointestinal Surgery, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China. FAU - Meng, Song AU - Meng S FAU - Jiang, Hong AU - Jiang H FAU - Zhu, Chunfu AU - Zhu C FAU - Wu, Wenxi AU - Wu W LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100608 PL - United States TA - J Surg Res JT - The Journal of surgical research JID - 0376340 RN - 0 (CD4 Antigens) RN - 0 (Forkhead Transcription Factors) RN - 0 (Foxp3 protein, rat) RN - 0 (Interleukin-2 Receptor alpha Subunit) SB - IM MH - Acute Disease MH - Animals MH - Bone Marrow Cells/*immunology MH - CD4 Antigens/metabolism MH - Dendritic Cells/*immunology MH - Exosomes/*immunology MH - Forkhead Transcription Factors/metabolism MH - Graft Rejection/immunology/prevention & control MH - Graft Survival/*immunology MH - Immune Tolerance/*immunology MH - Interleukin-2 Receptor alpha Subunit/metabolism MH - Intestines/*transplantation MH - Male MH - Rats MH - Rats, Inbred F344 MH - Spleen/cytology/immunology MH - T-Lymphocytes/immunology/metabolism MH - Transplantation, Homologous EDAT- 2010/09/11 06:00 MHDA- 2012/01/10 06:00 CRDT- 2010/09/11 06:00 PHST- 2010/01/13 00:00 [received] PHST- 2010/04/21 00:00 [revised] PHST- 2010/05/11 00:00 [accepted] PHST- 2010/09/11 06:00 [entrez] PHST- 2010/09/11 06:00 [pubmed] PHST- 2012/01/10 06:00 [medline] AID - S0022-4804(10)00472-5 [pii] AID - 10.1016/j.jss.2010.05.021 [doi] PST - ppublish SO - J Surg Res. 2011 Dec;171(2):826-32. doi: 10.1016/j.jss.2010.05.021. Epub 2010 Jun 8.