Rapid CommunicationsCCR9–Positive lymphocytes and thymus-expressed chemokine distinguish small bowel from colonic Crohn's disease☆,☆☆
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.
References (39)
- et al.
Current theories on the causes of inflammatory bowel disease
Gastroenterol Clin North Am
(1999) Inflammatory bowel disease: etiology and pathogenesis
Gastroenterology
(1998)- et al.
Impaired on/off regulation of TNF biosynthesis in mice lacking TNF AU-rich elements: implications for joint and gut-associated immunopathologies
Immunity
(1999) - et al.
Chemokines in inflammation and immunity
Immunol Today
(2000) - et al.
Regional specialization in the mucosal immune system: primed cells do not always home along the same track
Immunol Today
(1999) - et al.
Lymphocyte trafficking and regional immunity
Adv Immunol
(1999) - et al.
Chemokines in tissue-specific and microenvironment-specific lymphocyte homing
Curr Opin Immunol
(2000) - et al.
Regulated production of interferon-inducible T-cell chemoattractants by human intestinal epithelial cells
Gastroenterology
(2001) - et al.
Characterization of epithelial chemoattractants for human intestinal intraepithelial lymphocytes
Gastroenterology
(2001) - et al.
Differential and regulated expression of C-X-C, C-C, and C-chemokines by human colon epithelial cells
Gastroenterology
(1997)
Chemokines and chemokine receptors in T-cell priming and Th1/Th2-mediated responses
Immunol Today
TECK: a novel CC chemokine specifically expressed by thymic dendritic cells and potentially involved in T cell development
Immunity
Increased activation of isolated intestinal lamina propria mononuclear cells in inflammatory bowel disease
Gastroenterology
Regional expression of thymus expressed chemokine (TECK) and its receptor CCR9 in the small bowel: evidence for enhanced recirculation of CCR9+ lymphocytes in small bowel Crohn's disease
Gastroenterology
Monocyte-chemoattractant protein 1 gene expression in intestinal epithelial cells and inflammatory bowel disease mucosa
Gastroenterology
Experimental models to study molecular mechanisms underlying intestinal inflammation
Ann N Y Acad Sci
CD4+ T cells reactive to enteric bacterial antigens in spontaneously colitic C3H/HeJBir mice: increased T helper cell type 1 response and ability to transfer disease
J Exp Med
Human intestinal lamina propria and intraepithelial lymphocytes express receptors specific for chemokines induced by inflammation
Eur J Immunol
The central role of chemokines (chemotactic cytokines) in the immunopathogenesis of ulcerative colitis and Crohn's disease
Inflamm Bowel Dis
Cited by (191)
IL-36 cytokines imprint a colitogenic phenotype on CD4<sup>+</sup> T helper cells
2022, Mucosal ImmunologyTranscriptional regulation of chemokine network by biologic monotherapy in ileum of patients with Crohn's disease
2022, Biomedicine and PharmacotherapyLeukocyte trafficking to the intestinal barrier in health and disease
2022, Cell Movement in Health and DiseaseUsing evasins to target the chemokine network in inflammation
2020, Advances in Protein Chemistry and Structural Biology
- ☆
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.