Inhibition of Dectin-1 on Dendritic Cells Prevents Maturation and Prolongs Murine Islet Allograft Survival

Ao Ren,1– 3 Zhongqiu Li,1– 3 Xuzhi Zhang,1– 3 Ronghai Deng,1– 3 Yi Ma1– 3 1Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Organ...

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Autores principales:	Ren A, Li Z, Zhang X, Deng R, Ma Y
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	dendritic cell dectin-1 immune tolerance islet transplant lentiviral vector Pathology RB1-214 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/2ab24f92128b4cde98be9b5c5cd67960
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spelling	oai:doaj.org-article:2ab24f92128b4cde98be9b5c5cd679602021-12-02T15:14:37ZInhibition of Dectin-1 on Dendritic Cells Prevents Maturation and Prolongs Murine Islet Allograft Survival1178-7031https://doaj.org/article/2ab24f92128b4cde98be9b5c5cd679602021-01-01T00:00:00Zhttps://www.dovepress.com/inhibition-of-dectin-1-on-dendritic-cells-prevents-maturation-and-prol-peer-reviewed-article-JIRhttps://doaj.org/toc/1178-7031Ao Ren,1– 3 Zhongqiu Li,1– 3 Xuzhi Zhang,1– 3 Ronghai Deng,1– 3 Yi Ma1– 3 1Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 3Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of ChinaCorrespondence: Ronghai Deng; Yi MaOrgan Transplant Center, The First Affiliated Hospital, Sun Yat-sen university, No. 58 Zhongshan Er Road, Guangzhou 510080, People’s Republic of ChinaTel/Fax +86-20-87306082Email mddrh81@163.com; anhuimayi2002@163.comIntroduction: The ability of dendritic cells (DCs) to initiate an immune response or induce immune tolerance depends on their maturation status. Dendritic-cell-associated C-type lectin 1 (Dectin-1) plays a key role in the differentiation, activation, and maturation of DCs. Therefore, we hypothesized that inhibition of Dectin-1 could prevent DC maturation and induce immune tolerance of transplanted organs.Methods: DCs were transduced with a recombinant lentiviral vector to inhibit Dectin-1 and then were injected into a murine recipient before islet transplantation. C57BL/6 mice (H-2b) were treated with lentiviral vector-Dectin-1-RNAi-DC (DC-Dectin-1-RNAi group), lentiviral vector-GFP DCs (DC-GFP group), and PBS (control group). Pancreatic islet transplantation was performed and graft survival was recorded. The proportions of regulatory T cells, Th1 cells, and Th17 cells in the spleen and draining lymph nodes, and serum levels of interleukin (IL)-10, IL-17, and interferon (INF)-γ were measured.Results: The inhibition of Dectin-1 resulted in low expression of MHC-II and costimulatory molecules in DCs. Murine recipients treated with DC-Dectin-1-RNAi had longer islet allograft survival time, a reduction in the levels of Th1 and Th17 cells and secreted cytokines, and an increase of Treg cells.Conclusion: The inhibition of Dectin-1 by recombinant lentiviral vector Dectin-1-RNAi inhibits the maturation and activation of DCs, affects the differentiation of T cell subsets, and prolongs allograft survival.Keywords: dendritic cell, Dectin-1, immune tolerance, islet transplant, lentiviral vectorRen ALi ZZhang XDeng RMa YDove Medical Pressarticledendritic celldectin-1immune toleranceislet transplantlentiviral vectorPathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 14, Pp 63-73 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	dendritic cell dectin-1 immune tolerance islet transplant lentiviral vector Pathology RB1-214 Therapeutics. Pharmacology RM1-950
spellingShingle	dendritic cell dectin-1 immune tolerance islet transplant lentiviral vector Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Ren A Li Z Zhang X Deng R Ma Y Inhibition of Dectin-1 on Dendritic Cells Prevents Maturation and Prolongs Murine Islet Allograft Survival
description	Ao Ren,1– 3 Zhongqiu Li,1– 3 Xuzhi Zhang,1– 3 Ronghai Deng,1– 3 Yi Ma1– 3 1Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 3Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of ChinaCorrespondence: Ronghai Deng; Yi MaOrgan Transplant Center, The First Affiliated Hospital, Sun Yat-sen university, No. 58 Zhongshan Er Road, Guangzhou 510080, People’s Republic of ChinaTel/Fax +86-20-87306082Email mddrh81@163.com; anhuimayi2002@163.comIntroduction: The ability of dendritic cells (DCs) to initiate an immune response or induce immune tolerance depends on their maturation status. Dendritic-cell-associated C-type lectin 1 (Dectin-1) plays a key role in the differentiation, activation, and maturation of DCs. Therefore, we hypothesized that inhibition of Dectin-1 could prevent DC maturation and induce immune tolerance of transplanted organs.Methods: DCs were transduced with a recombinant lentiviral vector to inhibit Dectin-1 and then were injected into a murine recipient before islet transplantation. C57BL/6 mice (H-2b) were treated with lentiviral vector-Dectin-1-RNAi-DC (DC-Dectin-1-RNAi group), lentiviral vector-GFP DCs (DC-GFP group), and PBS (control group). Pancreatic islet transplantation was performed and graft survival was recorded. The proportions of regulatory T cells, Th1 cells, and Th17 cells in the spleen and draining lymph nodes, and serum levels of interleukin (IL)-10, IL-17, and interferon (INF)-γ were measured.Results: The inhibition of Dectin-1 resulted in low expression of MHC-II and costimulatory molecules in DCs. Murine recipients treated with DC-Dectin-1-RNAi had longer islet allograft survival time, a reduction in the levels of Th1 and Th17 cells and secreted cytokines, and an increase of Treg cells.Conclusion: The inhibition of Dectin-1 by recombinant lentiviral vector Dectin-1-RNAi inhibits the maturation and activation of DCs, affects the differentiation of T cell subsets, and prolongs allograft survival.Keywords: dendritic cell, Dectin-1, immune tolerance, islet transplant, lentiviral vector
format	article
author	Ren A Li Z Zhang X Deng R Ma Y
author_facet	Ren A Li Z Zhang X Deng R Ma Y
author_sort	Ren A
title	Inhibition of Dectin-1 on Dendritic Cells Prevents Maturation and Prolongs Murine Islet Allograft Survival
title_short	Inhibition of Dectin-1 on Dendritic Cells Prevents Maturation and Prolongs Murine Islet Allograft Survival
title_full	Inhibition of Dectin-1 on Dendritic Cells Prevents Maturation and Prolongs Murine Islet Allograft Survival
title_fullStr	Inhibition of Dectin-1 on Dendritic Cells Prevents Maturation and Prolongs Murine Islet Allograft Survival
title_full_unstemmed	Inhibition of Dectin-1 on Dendritic Cells Prevents Maturation and Prolongs Murine Islet Allograft Survival
title_sort	inhibition of dectin-1 on dendritic cells prevents maturation and prolongs murine islet allograft survival
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/2ab24f92128b4cde98be9b5c5cd67960
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Inhibition of Dectin-1 on Dendritic Cells Prevents Maturation and Prolongs Murine Islet Allograft Survival

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