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

被引:132
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
  • [41] A regulatory B cell subset with a unique CD1dhiCD5+ phenotype controls T cell-dependent inflammatory responses
    Yanaba, Koichi
    Bouaziz, Jean-David
    Haas, Karen M.
    Poe, Jonathan C.
    Fujimoto, Manabu
    Tedder, Thomas F.
    [J]. IMMUNITY, 2008, 28 (05) : 639 - 650
  • [42] B cell depletion delays collagen-induced arthritis in mice: Arthritis induction requires synergy between humoral and cell-mediated immunity
    Yanaba, Koichi
    Hamaguchi, Yasuhito
    Venturi, Guglielmo M.
    Steeber, Douglas A.
    St. Clair, E. William
    Tedder, Thomas F.
    [J]. JOURNAL OF IMMUNOLOGY, 2007, 179 (02) : 1369 - 1380
  • [43] The Development and Function of Regulatory B Cells Expressing IL-10 (B10 Cells) Requires Antigen Receptor Diversity and TLR Signals
    Yanaba, Koichi
    Bouaziz, Jean-David
    Matsushita, Takashi
    Tsubata, Takeshi
    Tedder, Thomas F.
    [J]. JOURNAL OF IMMUNOLOGY, 2009, 182 (12) : 7459 - 7472