CD44 isoform expression on colonic epithelium mediates lamina propria lymphocyte adhesion and is controlled by Th1 and Th2 cytokines.
OBJECTIVE
CD44v6 and CD44v3 are expressed on the surface of colonic epithelial cells in ulcerative colitis to a much greater extent than in Crohn's disease. We investigated mediators that induce CD44v6 and CD44v3 expression on colonic epithelium and the potential role of CD44 in mediating leucocyte-epithelial adhesion.


METHODS
HT-29 cells were exposed to a range of T-helper 1 and T-helper 2 cytokines. Flow cytometry was used to determine their effect on CD44 isoform expression. The adhesion of peripheral blood and lamina propria lymphocytes to HT-29 monolayers was assessed and the effect of induction and blocking of CD44 isoforms was investigated.


RESULTS
Treatment of HT-29 cells with IL-4 and IL-13 resulted in a two- to three-fold increase in membrane expression of CD44v6 and CD44v3 isoforms. This was inhibited by T-helper 1 cytokines and hydrocortisone (P < 0.001). IL-4 increased lymphocyte adhesion to HT-29 monolayers approximately two-fold (P < 0.01). This increased adhesion of both lamina propria leucocytes and peripheral blood lymphocytes was abolished by anti-CD44v6 monoclonal antibodies (P < 0.01 and P < 0.05, respectively).


CONCLUSIONS
IL-4 and IL-13 are potent inducers of CD44v6 and CD44v3 expression on colon epithelial cells. The reciprocal effects of T-helper 2 and T-helper 1 cytokines on CD44 isoform expression may explain the observed differences between ulcerative colitis and colonic Crohn's disease. We have identified increased adhesion between lymphocytes and colon epithelial cells caused by IL-4-induced CD44v6 expression. This may contribute to epithelial targeting of inflammation in ulcerative colitis.
D001485:Basement Membrane / Q000276:immunology; D002448:Cell Adhesion / Q000276:immunology; D003093:Colitis, Ulcerative / Q000276:immunology; D003106:Colon / Q000276:immunology*; D016207:Cytokines / Q000276:immunology*; D006023:Glycoproteins / Q000276:immunology / Q000378:metabolism*; D019073:HT29 Cells; D006801:Humans; D018960:Hyaluronan Receptors / Q000276:immunology / Q000378:metabolism*; D015212:Inflammatory Bowel Diseases / Q000276:immunology*; D018793:Interleukin-13 / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology
C121450:CD44V3,8-10; C112697:CD44v6 antigen; D016207:Cytokines; D006023:Glycoproteins; D018960:Hyaluronan Receptors; D018793:Interleukin-13; D015847:Interleukin-4