IL-21/anti-Tim1/CD40 ligand promotes B10 activity in vitro and alleviates bone loss in experimental periodontitis in vivo

被引:38
作者
Hu, Yang [1 ,2 ]
Yu, Pei [1 ,3 ]
Yu, Xinbo [1 ,4 ]
Hu, Xingxue [1 ]
Kawai, Toshihisa [1 ,2 ]
Han, Xiaozhe [1 ,2 ]
机构
[1] Forsyth Inst, Dept Immunol & Infect Dis, Cambridge, MA USA
[2] Harvard Univ, Sch Dent Med, Cambridge, MA 02138 USA
[3] Sichuan Univ, West China Sch Stomatol, State Key Lab Oral Dis, Chengdu, Sichuan, Peoples R China
[4] Qingdao Univ, Affiliated Hosp, Dept Periodontol, Qingdao, Shandong, Peoples R China
来源
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE | 2017年 / 1863卷 / 09期
关键词
Periodontitis; B10; IL-21; Anti-Tim1; IL-10; REGULATORY B-CELLS; IMMUNE CELLS; INFLAMMATION; IL-10; IL-21; TIM-1; MICE; MAINTENANCE; EXPRESSION; INDUCTION;
D O I
10.1016/j.bbadis.2017.06.001
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
IL-10-expressing regulatory B cells (B10) play an essential role in immune system balance by suppressing excessive inflammatory responses. In this study, we investigated induction of B 10 cell's IL-10 competency in vitro and its effect on ligature -induced experimental periodontitis in vivo. Spleen B cells were isolated from C57BL/6J mice and cultured for 48 h under the following conditions: control, CD40L, IL-21, anti-Tim1, CD4OL + IL-21, CD40L + anti-Tim1, CD40L + IL-21 + anti-Tim1. Silk ligatures were tied around both maxillary second molars of C57BL/6J mice for two weeks. Optimized combination of CD4OL, IL-21 and anti-Tim1 and vehicle were injected into contralateral side of palatal gingiva on days 3, 6 and 9. The palatal gingival tissues and maxillary bone were collected on day 14 to determine expressions of IL-10 and periodontal bone resorption respectively. Our results demonstrated that IL-10 expressions of cultured spleen B cells were significantly increased in the presence of CD4OL, IL-21 and anti-Tim1 combination when compared with control groups. Gingival IL-10 mRNA and protein expressions were significantly increased after injection of CD4OL, IL-21 and anti-Tim1 combination, when compared to the control side. The gingival RANKL, expression and periodontal bone loss were significantly decreased on the combination treatment side, as compared to the control side. These results suggest that combination of IL-21, anti-Tim1 and CD4OL treatment induced B10 cell's IL-10 competency in vitro and inhibited periodontal bone loss in ligature-induced experimental periodontitis.
引用
收藏
页码:2149 / 2157
页数:9
相关论文
共 42 条
[1]
Optimization of the ligature-induced periodontitis model in mice [J].
Abe, Toshiharu ;
Hajishengallis, George .
JOURNAL OF IMMUNOLOGICAL METHODS, 2013, 394 (1-2) :49-54
[2]
Generation of human B-cell lines dependent on CD40 ligation and interleukin-4 [J].
Banchereau, Jacques .
FRONTIERS IN IMMUNOLOGY, 2015, 6
[3]
Periodontitis and bone metabolism [J].
Barbato, Luigi ;
Francioni, Edoardo ;
Bianchi, Massimiliano ;
Mascitelli, Eleonora ;
Brancato, Leila ;
Duvina, Marco ;
Tonelli, Paolo .
CLINICAL CASES IN MINERAL AND BONE METABOLISM, 2015, 12 (02) :174-177
[4]
The CD40-CD154 interaction in B cell-T cell liaisons [J].
Bishop, GA ;
Hostager, BS .
CYTOKINE & GROWTH FACTOR REVIEWS, 2003, 14 (3-4) :297-309
[5]
B10 cell regulation of health and disease [J].
Candando, Kathleen M. ;
Lykken, Jacquelyn M. ;
Tedder, Thomas F. .
IMMUNOLOGICAL REVIEWS, 2014, 259 (01) :259-272
[6]
TLR-CD40 cross-talk in anti-leishmanial immune response [J].
Chandel, Himanshu Singh ;
Pandey, Surya Prakash ;
Roy, Sayoni ;
Doyen, Noelle ;
Saha, Bhaskar .
FRONTIERS IN IMMUNOLOGY, 2014, 5
[7]
A short history of the B-cell-associated surface molecule CD40 [J].
Clark, Edward A. .
FRONTIERS IN IMMUNOLOGY, 2014, 5
[8]
T-cell Expression of IL10 Is Essential for Tumor Immune Surveillance in the Small Intestine [J].
Dennis, Kristen L. ;
Saadalla, Abdulrahman ;
Blatner, Nichole R. ;
Wang, Shuya ;
Venkateswaran, Vysak ;
Gounari, Fotini ;
Cheroutre, Hilde ;
Weaver, Casey T. ;
Roers, Axel ;
Egilmez, Nejat K. ;
Khazaie, Khashayarsha .
CANCER IMMUNOLOGY RESEARCH, 2015, 3 (07) :806-814
[9]
B10 cells and regulatory B cells balance immune responses during inflammation, autoimmunity, and cancer [J].
DiLillo, David J. ;
Matsushita, Takashi ;
Tedder, Thomas F. .
YEAR IN IMMUNOLOGY 2, 2010, 1183 :38-57
[10]
Regulatory B cells are identified by expression of TIM-1 and can be induced through TIM-1 ligation to promote tolerance in mice [J].
Ding, Qing ;
Yeung, Melissa ;
Camirand, Geoffrey ;
Zeng, Qiang ;
Akiba, Hisaya ;
Yagita, Hideo ;
Chalasani, Geetha ;
Sayegh, Mohamed H. ;
Najafian, Nader ;
Rothstein, David M. .
JOURNAL OF CLINICAL INVESTIGATION, 2011, 121 (09) :3645-3656