IL-10-Producing Regulatory B10 Cells Inhibit Intestinal Injury in a Mouse Model

被引:135
作者
Yanaba, Koichi [2 ]
Yoshizaki, Ayumi [3 ]
Asano, Yoshihide
Kadono, Takafumi
Tedder, Thomas F. [4 ]
Sato, Shinichi [1 ]
机构
[1] Univ Tokyo, Fac Med, Dept Dermatol, Bunkyo Ku, Tokyo 1138655, Japan
[2] Jikei Univ, Sch Med, Dept Dermatol, Tokyo, Japan
[3] Nagasaki Univ, Grad Sch Biomed Sci, Dept Dermatol, Nagasaki 852, Japan
[4] Duke Univ, Med Ctr, Dept Immunol, Durham, NC USA
基金
美国国家卫生研究院;
关键词
B-LYMPHOCYTE DEPLETION; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; INFLAMMATORY-BOWEL-DISEASE; ULCERATIVE-COLITIS; T-CELLS; B-1B CELLS; MICE; CD19; ACTIVATION; INITIATION;
D O I
10.1016/j.ajpath.2010.10.022
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
B cells mediate multiple functions that influence immune and inflammatory responses. In mice, the addition of dextran sulfate sodium (DSS) to drinking water leads to immediate intestinal injury. Dextran sulfate sodium-induced intestinal injury serves as an experimental animal model for human ulcerative colitis. The contribution of B cells to DSS-induced intestinal injury is unclear. In this study, we show that DSS-induced intestinal injury was more severe in CD19-deficient (CD19(-/-)) mice than in wild-type mice. These inflammatory responses were negatively regulated by a unique IL-10-producing CD1d(hl)CD5(+) regulatory B cell subset (B10 cells) that was absent in CD19(-/-) mice and represented only 1% to 2% of splenic B220(+) cells in wild-type mice. Remarkably, adoptive transfer of these B10 cells from wild-type mice reduced inflammation in CD19(-/-) mice in an IL-10-dependent manner. These results demonstrate that IL-10 production from regulatory B10 cells regulates DSS-induced intestinal injury. These findings may provide new insights and therapeutic approaches for treating ulcerative colitis. (Am J Pathol 2011, 178:735-743; DOI: 10.1016/j.ajpath.2010.10.022)
引用
收藏
页码:735 / 743
页数:9
相关论文
共 43 条
[1]   Regulatory B cells as inhibitors of immune responses and inflammation [J].
Bouaziz, Jean-David ;
Yanaba, Koichi ;
Tedder, Thomas F. .
IMMUNOLOGICAL REVIEWS, 2008, 224 :201-214
[2]   Therapeutic B cell depletion impairs adaptive and autoreactive CD4+ T cell activation in mice [J].
Bouaziz, Jean-David ;
Yanaba, Koichi ;
Venturi, Guglielmo M. ;
Wang, Yaming ;
Tisch, Roland M. ;
Poe, Jonathan C. ;
Tedder, Thomas F. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (52) :20878-20883
[3]   Activation of marginal zone B cells from lupus mice with type A(D) CpG-oligodeoxynucleotides [J].
Brummel, R ;
Lenert, P .
JOURNAL OF IMMUNOLOGY, 2005, 174 (04) :2429-2434
[4]  
CONSTANT S, 1995, J IMMUNOL, V155, P3734
[5]  
COOPER HS, 1993, LAB INVEST, V69, P238
[6]   B cell developmental requirement for the Gαi2 gene [J].
Dalwadi, H ;
Wei, B ;
Schrage, M ;
Su, TT ;
Rawlings, DJ ;
Braun, J .
JOURNAL OF IMMUNOLOGY, 2003, 170 (04) :1707-1715
[7]   Characterisation of acute murine dextran sodium sulphate colitis:: Cytokine profile and dose dependency [J].
Egger, B ;
Bajaj-Elliott, M ;
MacDonald, TT ;
Inglin, R ;
Eysselein, VE ;
Büchler, MW .
DIGESTION, 2000, 62 (04) :240-248
[8]  
El Fassi D, 2008, GUT, V57, P714, DOI 10.1136/gut.2007.138305
[9]   ABNORMAL B-LYMPHOCYTE DEVELOPMENT, ACTIVATION, AND DIFFERENTIATION IN MICE THAT LACK OR OVEREXPRESS THE CD19 SIGNAL-TRANSDUCTION MOLECULE [J].
ENGEL, P ;
ZHOU, LJ ;
ORD, DC ;
SATO, S ;
KOLLER, B ;
TEDDER, TF .
IMMUNITY, 1995, 3 (01) :39-50
[10]   B cells regulate autoimmunity by provision of IL-10 [J].
Fillatreau, S ;
Sweenie, CH ;
McGeachy, MJ ;
Gray, D ;
Anderton, SM .
NATURE IMMUNOLOGY, 2002, 3 (10) :944-950