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CD44 isoform expression on colonic epithelium mediates lamina propria lymphocyte adhesion and is controlled by Th1 and Th2 cytokines

CD44 isoform expression on colonic epithelium mediates lamina propria lymphocyte adhesion and is controlled by Th1 and Th2 cytokines
CD44 isoform expression on colonic epithelium mediates lamina propria lymphocyte adhesion and is controlled by Th1 and Th2 cytokines
Background and aims: 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.
Design and 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).
Conclusion: 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.
0954-691X
1101-1110
Macdonald, Douglas C.
21fdfc3b-0b61-418b-a702-ce758d6fc7c0
Leir, Shih-Hsing
c534558c-19b3-409c-afcc-fedc66e1e3e5
Brooks, Corrine
3ad1acfe-65ca-4cb3-ad2a-c91407a8f189
Sanders, Elizabeth
d9d32d1a-2212-432d-b280-c1909e991ae0
Lackie, Peter
4afbbe1a-22a6-4ceb-8cad-f3696dc43a7a
Rosenberg, William
cea47565-06a3-4622-931c-aa5a7686865c
Macdonald, Douglas C.
21fdfc3b-0b61-418b-a702-ce758d6fc7c0
Leir, Shih-Hsing
c534558c-19b3-409c-afcc-fedc66e1e3e5
Brooks, Corrine
3ad1acfe-65ca-4cb3-ad2a-c91407a8f189
Sanders, Elizabeth
d9d32d1a-2212-432d-b280-c1909e991ae0
Lackie, Peter
4afbbe1a-22a6-4ceb-8cad-f3696dc43a7a
Rosenberg, William
cea47565-06a3-4622-931c-aa5a7686865c

Macdonald, Douglas C., Leir, Shih-Hsing, Brooks, Corrine, Sanders, Elizabeth, Lackie, Peter and Rosenberg, William (2003) CD44 isoform expression on colonic epithelium mediates lamina propria lymphocyte adhesion and is controlled by Th1 and Th2 cytokines. European Journal of Gastroenterology & Hepatology, 15 (10), 1101-1110.

Record type: Article

Abstract

Background and aims: 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.
Design and 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).
Conclusion: 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.

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Published date: 2003

Identifiers

Local EPrints ID: 27246
URI: http://eprints.soton.ac.uk/id/eprint/27246
ISSN: 0954-691X
PURE UUID: ffdbbaa0-15ec-403d-8af3-1834a296aed5
ORCID for Peter Lackie: ORCID iD orcid.org/0000-0001-7138-3764

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Date deposited: 28 Apr 2006
Last modified: 09 Jan 2022 02:45

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Contributors

Author: Douglas C. Macdonald
Author: Shih-Hsing Leir
Author: Corrine Brooks
Author: Elizabeth Sanders
Author: Peter Lackie ORCID iD
Author: William Rosenberg

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