Downregulating galectin-3 inhibits proinflammatory cytokine production by human monocyte-derived dendritic cells via RNA interference

被引：64
作者：
Chen, Swey-Shen [1 ,2 ,3 ]
Sun, Liang-Wu [1 ,2 ]
Brickner, Howard [1 ,2 ]
Sun, Pei-Qing [3 ]
机构：
[1] Inst Genet, Dept Immunol, San Diego, CA USA
[2] IGE Therapeut Inc, Dept Allergy Inflammat & Vaccinol, San Diego, CA 92121 USA
[3] Scripps Res Inst, Dept Cell & Mol Biol, La Jolla, CA 92037 USA
来源：
CELLULAR IMMUNOLOGY | 2015年 / 294卷 / 01期
关键词：
Galectin-3; Th17; Dendritic cells; Inflammation; Cytokines; Innate immunity; T-CELLS; INTERLEUKIN; 27; TGF-BETA; ACTIVATION; STIMULATION; EXPRESSION; RECEPTORS; INFECTION; ALLERGEN; ASTHMA;
D O I：
10.1016/j.cellimm.2015.01.017
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
Galectin-3 (Gal-3), a B-galactoside-binding lectin, serves as a pattern-recognition receptor (PRR) of dendritic cells (DCs) in regulating proinflammatory cytokine production. Galectin-3 (Gal-3) siRNA downregulates expression of IL-6, IL-1 beta and IL-23 p19, while upregulates IL-10 and IL-12 p35 in TLR/NLR stimulated human MoDCs. Furthermore, Gal-3 siRNA-treated MoDCs enhanced IFN-gamma production in SEB-stimulated CD45RO CD4 T-cells, but attenuated IL-17A and IL-5 production by CD4 T-cells. Addition of neutralizing antibodies against Gal-3, or recombinant Gal-3 did not differentially modulate IL-23 p19 versus IL-12 p35. The data indicate that intracellular Gal-3 acts as cytokine hub of human DCs in responding to innate immunity signals. Gal-3 downregulation reprograms proinflammatory cytokine production by MoDCs that inhibit Th2/Th17 development. (C)2015 Elsevier Inc. All rights reserved.
引用
收藏
页码：44 / 53
页数：10
相关论文
共 59 条
[1]   Do studies in humans better depict Th17 cells? [J].
Annunziato, Francesco ;
Romagnani, Sergio .
BLOOD, 2009, 114 (11) :2213-2219
[2]   Dectin-2 Recognition of House Dust Mite Triggers Cysteinyl Leukotriene Generation by Dendritic Cells [J].
Barrett, Nora A. ;
Maekawa, Akiko ;
Rahman, Opu M. ;
Austen, K. Frank ;
Kanaoka, Yoshihide .
JOURNAL OF IMMUNOLOGY, 2009, 182 (02) :1119-1128
[3]   Intranasally delivered siRNA targeting PI3K/Akt/mTOR inflammatory pathways protects from aspergillosis [J].
Bonifazi, P. ;
D'Angelo, C. ;
Zagarella, S. ;
Zelante, T. ;
Bozza, S. ;
De Luca, A. ;
Giovannini, G. ;
Moretti, S. ;
Iannitti, R. G. ;
Fallarino, F. ;
Carvalho, A. ;
Cunha, C. ;
Bistoni, F. ;
Romani, L. .
MUCOSAL IMMUNOLOGY, 2010, 3 (02) :193-205
[4]   Repression of the antiapoptotic molecule galectin-3 by homeodomain-interacting protein kinase 2-activated p53 is required for p53-induced apoptosis [J].
Cecchinelli, Barbara ;
Lavra, Luca ;
Rinaldo, Cinzia ;
Iacovelli, Stefano ;
Gurtner, Aymone ;
Gasbarri, Alessandra ;
Ulivieri, Alessandra ;
Del Prete, Fabrizio ;
Trovato, Maria ;
Piaggio, Giulia ;
Bartolazzi, Armando ;
Soddu, Silvia ;
Sciacchitano, Salvatore .
MOLECULAR AND CELLULAR BIOLOGY, 2006, 26 (12) :4746-4757
[5]  
Chen S.S., 2013, RNA interference of galectin-3 expression and the methods of use thereof, Patent No. [US 2013/0072540 Al, 20130072540]
[6]   Microbial Stimulation Fully Differentiates Monocytes to DC-SIGN/CD209+ Dendritic Cells for Immune T Cell Areas [J].
Cheong, Cheolho ;
Matos, Ines ;
Choi, Jae-Hoon ;
Dandamudi, Durga Bhavani ;
Shrestha, Elina ;
Longhi, M. Paula ;
Jeffrey, Kate L. ;
Anthony, Robert M. ;
Kluger, Courtney ;
Nchinda, Godwin ;
Koh, Hyein ;
Rodriguez, Anthony ;
Idoyaga, Juliana ;
Pack, Maggi ;
Velinzon, Klara ;
Park, Chae Gyu ;
Steinman, Ralph M. .
CELL, 2010, 143 (03) :416-429
[7]   The E3 ubiquitin ligase midline 1 promotes allergen and rhinovirus-induced asthma by inhibiting protein phosphatase 2A activity [J].
Collison, Adam ;
Hatchwell, Luke ;
Verrills, Nicole ;
Wark, Peter A. B. ;
de Siqueira, Ana Pereira ;
Tooze, Melinda ;
Carpenter, Helen ;
Don, Anthony S. ;
Morris, Jonathan C. ;
Zimmermann, Nives ;
Bartlett, Nathan W. ;
Rothenberg, Marc E. ;
Johnston, Sebastian L. ;
Foster, Paul S. ;
Mattes, Joerg .
NATURE MEDICINE, 2013, 19 (02) :232-237
[8]   Galectin-3: a novel mediator of heart failure development and progression [J].
de Boer, Rudolf A. ;
Voors, Adriaan A. ;
Muntendam, Pieter ;
van Gilst, Wiek H. ;
van Veldhuisen, Dirk J. .
EUROPEAN JOURNAL OF HEART FAILURE, 2009, 11 (09) :811-817
[9]   Negative regulation of T-cell activation and autoimmunity by Mgat5 N-glycosylation [J].
Demetriou, M ;
Granovsky, M ;
Quaggin, S ;
Dennis, JW .
NATURE, 2001, 409 (6821) :733-739
[10]   BDCA-2, BDCA-3 and BDCA-4: Three markers for distinct subsets of dendritic cells in human peripheral blood [J].
Dzionek, A ;
Fuchs, A ;
Schmidt, P ;
Cremer, S ;
Zysk, M ;
Miltenyi, S ;
Buck, DW ;
Schmitz, J .
JOURNAL OF IMMUNOLOGY, 2000, 165 (11) :6037-6046
123456