Gastroenterology

Gastroenterology

Volume 121, Issue 2, August 2001, Pages 246-254
Gastroenterology

Rapid Communications
CCR9–Positive lymphocytes and thymus-expressed chemokine distinguish small bowel from colonic Crohn's disease,☆☆

Part of this work was presented at the 2000 Digestive Disease Week (DDW), San Diego, California, American Gastroenterological Association, and the 2000 American Association of Immunologists/Clinical Immunology Society Meeting, Seattle, Washington.
https://doi.org/10.1053/gast.2001.27154Get rights and content

Abstract

Background & Aims: Thymus-expressed chemokine (TECK) or CCL25) is selectively expressed in the small bowel (SB), where lamina propria lymphocytes (LPL) and intraepithelial leukocyte expressing the cognate chemokine receptor CCR9 predominate.We characterize the role of TECK and CCR9-expresing lymphocytes in small intestinal Crohn's disease.Methods: CCR9 expression on lymphocytes from lamina propria, mesenteric lymph node, and peripheral blood was analyzed by flow cytometry and by Northern blotting for LPL.TECK expression was analyzed in inflamed SB and colon by reverse-transcription polymerase chain reaction and immunohistochemistry.Results: The fraction of CCR9+ T cells in inflamed SB was significantly lower than in uninvolved SB mucosa.In contrast, in peripheral blood lymphocytes, CCR9+ lymphocytes were markedly elevated in patients with small bowel Crohn's or celiac disease, but not in patients with purely colonic Crohn's.Also, TECK expression is altered in inflamed small bowel, being intensely expressed in a patchy distribution in crypt epithelial cells in proximity to lymphocytic infiltrates.TECK is not expressed in either normal or inflamed colon.Conclusions: In SB immune-mediated diseases, there is repartitioning of CCR9+ lymphocytes between SB and blood and an altered pattern of TECK expression in SB Crohn's.The TECK/CCR9 ligand/receptor pair may play an important role in the pathogenesis of SB Crohn's disease.

GASTROENTEROLOGY 2001;121:246-254

Section snippets

Purification of lamina propria, mesenteric lymph node, and peripheral blood mononuclear cells

Intestinal specimens were obtained from patients undergoing surgical resection of the colon for treatment-resistant UC or Crohn's colitis or small intestine for treatment refractory CD at Cedars-Sinai Medical Center, Los Angeles, CA.Approval for the use of human subjects was obtained from the Institutional Review Board at Cedars-Sinai Medical Center.In this study, all tissue specimens were taken from a macroscopically involved or uninvolved area of resected colon or small bowel when

The chemokine receptor CCR9 is expressed on a lower percentage of lymphocytes isolated from inflamed compared with uninvolved small bowel mucosa

We, and others, have previously shown that CCR9 is expressed on the majority of small bowel lymphocytes, but on a much smaller percentage in colon.23, 25 Approximately 67% (range, 57%–76%) of CD3+CD4+ SB lymphocytes isolated from ileum express CCR9 compared with 20% (range, 15%–25%) of CD3+CD4+ colonic lymphocytes.Similarly, CCR9 was expressed on 58% (range, 47%–70%) of CD3+CD8+ SB vs.10% (range, 6%–14%) of CD3+CD8+ colonic lymphocytes.25 Kunkel et al.have shown an even higher percentage of CCR9

Discussion

Antigen-reactive memory/effector cells induced in response to intestinal immunization traffic preferentially into the intestinal wall and/or into the intestine-associated lymphoid organs.8, 9, 32, 33, 34 T-cell homing to the intestinal lamina propria has been shown to be mediated by binding of α4β7 integrin on the lymphocyte surface to its vascular ligand, MAdCAM-1, thus providing a mechanism for the segregation of intestinal from systemic immune responses.We, and others, have recently proposed

Acknowledgements

The authors thank Phillip Fleshner, Joanne Gaiennie for providing specimens, Krystine Nguyen for isolating lamina propria mononuclear cells, Patricia Lin for flow cytometry, and Nassim Kassam for help and advice in generating the anti-TECK mAb 5A9.We also thank Loren Karp for critical reading of the manuscript.

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    Address requests for reprints to: Konstantinos A.Papadakis, M.D., or Stephan R.Targan, M.D., Inflammatory Bowel Disease Center, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, D-4063, Los Angeles, California 90048.e-mail: [email protected] or [email protected]; fax: (310) 423-0224.

    ☆☆

    Supported by National Institutes of Health grants DK-46763 and DK-56328.

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