TY - JOUR
T1 - Induced reactivity of intestinal CD4+ T cells with an epithelial cell lectin, galectin-4, contributes to exacerbation of intestinal inflammation
AU - Hokama, Akira
AU - Mizoguchi, Emiko
AU - Sugimoto, Ken
AU - Shimomura, Yasuyo
AU - Tanaka, Yosuke
AU - Yoshida, Masaru
AU - Rietdijk, Svend T.
AU - De Jong, Ype P.
AU - Snapper, Scott B.
AU - Terhorst, Cox
AU - Blumberg, Richard S.
AU - Mizoguchi, Atsushi
N1 - Funding Information:
We greatly thank Dr. D.R. Littman for kindly providing excellent advice for this manuscript and PKCθ KO mice; Dr. A.K. Bhan for his critical review of this manuscript; and Drs. V. Heissmeyer and A. Rao for kindly providing a mouse colony. A.M. was supported by NIH RO1DK064351, by First Award, Crohn's & Colitis Foundation of America, and by Pilot Feasibility grant (DK43351C11) of Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital. R.S.B. was supported by NIH RO1 DK44319, DK57362, DK 53056, and Harvard Digestive Disease Center. E.M. was supported by NIH KO8DK64289 and the Eli and Edythe L. Broad Medical Foundation.
PY - 2004/6
Y1 - 2004/6
N2 - 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 PKCθ-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.
AB - 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 PKCθ-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.
UR - http://www.scopus.com/inward/record.url?scp=2942617342&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=2942617342&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2004.05.009
DO - 10.1016/j.immuni.2004.05.009
M3 - Article
C2 - 15189734
AN - SCOPUS:2942617342
SN - 1074-7613
VL - 20
SP - 681
EP - 693
JO - Immunity
JF - Immunity
IS - 6
ER -