Induced reactivity of intestinal CD4+ T cells with an epithelial cell lectin, galectin-4, contributes to exacerbation of intestinal inflammation

被引:124
作者
Hokama, A
Mizoguchi, E
Sugimoto, K
Shimomura, Y
Tanaka, Y
Yoshida, M
Rietdijk, ST
de Jong, YP
Snapper, SB
Terhorst, C
Blumberg, RS
Mizoguchi, A [1 ]
机构
[1] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA
[2] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA
[3] Massachusetts Gen Hosp, Ctr Study Inflammat Bowel Dis, Boston, MA 02114 USA
[4] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA
[5] Beth Israel Deaconess Med Ctr, Div Immunol, Boston, MA USA
[6] Harvard Univ, Sch Med, Dept Pathol & Med, Boston, MA USA
关键词
D O I
10.1016/j.immuni.2004.05.009
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Inflammatory bowel disease is an immune-mediated intestinal inflammatory condition that is associated with an increase in autoantibodies that bind to epithelial cells. However, it is unknown whether the epithelial cell-derived products that are recognized by such autoantibodies are involved in the pathogenic process. Through a combined antigen-screening approach utilizing humoral and cellular immune responses, we identify herein an epithelial lectin, galectin-4, that specifically stimulates IL-6 production by CD4(+) T cells. Interestingly, the reactivity of CD4(+) T cells to galectin-4 is precisely elicited under intestinal inflammatory conditions. The galectin-4-mediated production of IL-6 is MHC class II independent and induced by PKCtheta-associated pathway through the immunological synapse. The galectin-4-mediated stimulation of CD4(+) T cells is shown to exacerbate chronic colitis and delay the recovery from acute intestinal injury. These studies identify the presence of an immunogenic, endogenous lectin in the intestine and dissect the biological role of lectin/CD4(+) T cell interactions under inflammatory conditions.
引用
收藏
页码:681 / 693
页数:13
相关论文
共 63 条
[1]   Protein kinase C-θ:: signaling from the center of the T-cell synapse [J].
Arendt, CW ;
Albrecht, B ;
Soos, TJ ;
Littman, DR .
CURRENT OPINION IN IMMUNOLOGY, 2002, 14 (03) :323-330
[2]   Blockade of interleukin 6 trans signaling suppresses T-cell resistance against apoptosis in chronic intestinal inflammation:: Evidence in Crohn disease and experimental colitis in vivo [J].
Atreya, R ;
Mudter, J ;
Finotto, S ;
Müllberg, J ;
Jostock, T ;
Wirtz, S ;
Schütz, M ;
Bartsch, B ;
Holtmann, M ;
Becker, C ;
Strand, D ;
Czaja, J ;
Schlaak, JF ;
Lehr, HA ;
Autschbach, F ;
Schürmann, G ;
Nishimoto, N ;
Yoshizaki, K ;
Ito, H ;
Kishimoto, T ;
Galle, PR ;
Rose-John, S ;
Neurath, MF .
NATURE MEDICINE, 2000, 6 (05) :583-588
[3]   GALECTINS - A FAMILY OF ANIMAL BETA-GALACTOSIDE-BINDING LECTINS [J].
BARONDES, SH ;
CASTRONOVO, V ;
COOPER, DNW ;
CUMMINGS, RD ;
DRICKAMER, K ;
FEIZI, T ;
GITT, MA ;
HIRABAYASHI, J ;
HUGHES, C ;
KASAI, K ;
LEFFLER, H ;
LIU, FT ;
LOTAN, R ;
MERCURIO, AM ;
MONSIGNY, M ;
PILLAI, S ;
POIRER, F ;
RAZ, A ;
RIGBY, PWJ ;
RINI, JM ;
WANG, JL .
CELL, 1994, 76 (04) :597-598
[4]   Developing a taste for sweets [J].
Baum, LG .
IMMUNITY, 2002, 16 (01) :5-8
[5]   The p38/RK mitogen-activated protein kinase pathway regulates interleukin-6 synthesis in response to tumour necrosis factor [J].
Beyaert, R ;
Cuenda, A ;
VandenBerghe, W ;
Plaisance, S ;
Lee, JC ;
Haegeman, G ;
Cohen, P ;
Fiers, W .
EMBO JOURNAL, 1996, 15 (08) :1914-1923
[6]   Colitis in transgenic and knockout animals as models of human inflammatory bowel disease [J].
Bhan, AK ;
Mizoguchi, E ;
Smith, RN ;
Mizoguchi, A .
IMMUNOLOGICAL REVIEWS, 1999, 169 :195-207
[7]   Microvillar membrane Microdomains exist at physiological temperature - Role of galectin-4 as lipid raft stabilizer revealed by "superrafts" [J].
Braccia, A ;
Villani, M ;
Immerdal, L ;
Niels-Christiansen, LL ;
Nystrom, BT ;
Hansen, GH ;
Danielsen, EM .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (18) :15679-15684
[8]   Quantitative imaging of raft accumulation in the immunological synapse [J].
Burack, WR ;
Lee, KH ;
Holdorf, AD ;
Dustin, ML ;
Shaw, AS .
JOURNAL OF IMMUNOLOGY, 2002, 169 (06) :2837-2841
[9]   Galectin-1 induces partial TCR ζ-chain phosphorylation and antagonizes processive TCR signal transduction [J].
Chung, CD ;
Patel, VP ;
Moran, M ;
Lewis, LA ;
Miceli, MC .
JOURNAL OF IMMUNOLOGY, 2000, 165 (07) :3722-3729
[10]   MASP-3 and its association with distinct complexes of the mannan-binding lectin complement activation pathway [J].
Dahl, MR ;
Thiel, S ;
Matsushita, M ;
Fujita, T ;
Willis, AC ;
Christensen, T ;
Vorup-Jensen, T ;
Jensenius, JC .
IMMUNITY, 2001, 15 (01) :127-135