Concurrent CCR7 Overexpression and RelB Knockdown in Immature Dendritic Cells Induces Immune Tolerance and Improves Skin-Graft Survival in a Murine Model

被引：15

作者：

Dong, Zhiwei ^{[1
]}

Chen, Yajie ^{[1
]}

Peng, Yuan ^{[3
]}

Wang, Fan ^{[4
]}

Yang, Zichen ^{[1
]}

Huang, Guangtao

Chen, Yu ^{[1
]}

Yuan, Zhiqiang ^{[1
]}

Cao, Tongtong ^{[2
]}

Peng, Yizhi ^{[1
]}

机构：

[1] Third Mil Med Univ, Southwest Hosp, State Key Lab Trauma Burns & Combined Injury, Inst Burn Res, Chongqing, Peoples R China

[2] Shanghai Univ Tradit Chinese Med, Dept Pathol, 1200Cailun Rd, Shanghai, Peoples R China

[3] Chongqing Med Univ, Clin Coll 1, Chongqing, Peoples R China

[4] Third Mil Med Univ Chongqing, Dept Plast & Reconstruct Surg, Southwest Hosp, Chongqing, Peoples R China

来源：

CELLULAR PHYSIOLOGY AND BIOCHEMISTRY | 2017年 / 42卷 / 02期

关键词：

imDCs; Treg cells; CCR7; RelB; Immune tolerance; Transplantation; REGULATORY T-CELLS; EXCHANGER; PATHWAY; IL-23;

D O I：

10.1159/000477593

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Background/Aims: Skin transplantation aims to cover skin defects but often fails due to immune rejection of the transplantated tissue. Immature dendritic cells (imDCs) induce immune tolerance but have a low migration rate. After stimulation, imDCs transform into mature DCs, which activate immune rejection. Thus, inducing imDC to obtain a high migration counteracts development of immune tolerance. Methods & Results: We transfected imDCs with a recombinant adenovirus carrying the CCR7 gene (Ad-CCR7) and a small interfering RNA targeting RelB (RelB-siRNA) to concurrently overexpress CCR7 and downregulate RelB expression. Functionally, such cells showed a significantly enhanced migration rate in the chemotactic assay and decreased T-cell proliferation after lipopolysaccharide stimulation in mixed lymphocyte reactions. Cotransfected cells showed an increased ability to induce immune tolerance by upregulating T regulatory (Treg) cells and shifting the Th1/Th2 ratio. Cotransfection of Ad-CCR7 and RelB-siRNA endowed imDCs with resistance to apoptosis and cell death. CCR7 overexpression and RelB knockdown (KD) in imDCs improve skin-graft survival in a murine skin-transplantation model. Conclusion: Transfection with Ad-CCR7 and RelB KD in imDCs may be an effective approach inducing immune tolerance, thus being potentially valuable for inhibiting allograft rejection. (C) 2017 The Author(s) Published by S. Karger AG, Basel

引用

页码：455 / 468

页数：14

共 28 条

[1] Quantitative Determination of Ceramide Molecular Species in Dendritic Cells [J].

Al Makdessi, Samar ;

Sweidan, Hicham ;

Schmid, Evi ;

Weimar, Udo ;

Gulbins, Erich ;

Lang, Florian .

CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, 2016, 39 (04) :1608-1617

[2] Homeostatic NF-κB Signaling in Steady-State Migratory Dendritic Cells Regulates Immune Homeostasis and Tolerance [J].

Baratin, Myriam ;

Foray, Chloe ;

Demaria, Olivier ;

Habbeddine, Mohamed ;

Pollet, Emeline ;

Maurizio, Julien ;

Verthuy, Christophe ;

Davanture, Suzel ;

Azukizawa, Hiroaki ;

Flores-Langarica, Adriana ;

Dalod, Marc ;

Lawrence, Toby .

IMMUNITY, 2015, 42 (04) :627-639

[3] Deficiency of Bim in dendritic cells contributes to overactivation of lymphocytes and autoimmunity [J].

Chen, Min ;

Huang, Li ;

Wang, Jin .

BLOOD, 2007, 109 (10) :4360-4367

[4] CCR7-Dependent Stimulation of Survival in Dendritic Cells Involves Inhibition of GSK3β [J].

Escribano, Cristina ;

Delgado-Martin, Cristina ;

Luis Rodriguez-Fernandez, Jose .

JOURNAL OF IMMUNOLOGY, 2009, 183 (10) :6282-6295

[5] IFN Regulatory Factor-1 Modulates the Function of Dendritic Cells in Patients with Acute Coronary Syndrome [J].

Guo, Min ;

Yan, Rui ;

Wang, Caixia ;

Shi, Hongtao ;

Sun, Meng ;

Guo, Shuang ;

Xiao, Chuanshi .

CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, 2015, 36 (02) :599-610

[6] Blockade of CCR7 leads to decreased dendritic cell migration to draining lymph nodes and promotes graft survival in low-risk corneal transplantation [J].

Hos, D. ;

Doerrie, J. ;

Schaft, N. ;

Bock, F. ;

Notara, M. ;

Kruse, F. E. ;

Krautwald, S. ;

Cursiefen, C. ;

Bachmann, B. O. .

EXPERIMENTAL EYE RESEARCH, 2016, 146 :1-6

[7] Homing of Regulatory T Cells to Human Skin Is Important for the Prevention of Alloimmune-Mediated Pathology in an In Vivo Cellular Therapy Model [J].

Issa, Fadi ;

Hester, Joanna ;

Milward, Kate ;

Wood, Kathryn J. .

PLOS ONE, 2012, 7 (12)

[8] Role of CCR7 in Facilitating Direct Allosensitization and Regulatory T-Cell Function in High-Risk Corneal Transplantation [J].

Jin, Yiping ;

Chauhan, Sunil K. ;

Saban, Daniel R. ;

Dana, Reza .

INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2010, 51 (02) :816-821

[9] Cisplatin induces tolerogenic dendritic cells in response to TLR agonists via the abundant production of IL-10, thereby promoting Th2-and Tr1-biased T-cell immunity [J].

Kim, Woo Sik ;

Kim, Hongmin ;

Kwon, Kee Woong ;

Im, Sin-Hyeog ;

Lee, Bo Ryeong ;

Ha, Sang-Jun ;

Shin, Sung Jae .

ONCOTARGET, 2016, 7 (23) :33765-33782

[10] CCR7 ligands up-regulate IL-23 through PI3-kinase and NF-κB pathway in dendritic cells [J].

Kuwabara, Taku ;

Tanaka, Yuriko ;

Ishikawa, Fumio ;

Kondo, Motonari ;

Sekiya, Hideki ;

Kakiuchi, Terutaka .

JOURNAL OF LEUKOCYTE BIOLOGY, 2012, 92 (02) :309-318

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