Phenotype and effector function of CC chemokine receptor 9-expressing lymphocytes in small intestinal Crohn's disease
| Autor: | Konstantinos A. Papadakis, Armine Avanesyan, Phillip Fleshner, Stephan R. Targan, Masayuki Saruta, Qi T. Yu |
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| Rok vydání: | 2007 |
| Předmět: |
Male
Chemokine medicine.medical_treatment Receptors Antigen T-Cell alpha-beta T-Lymphocytes Immunology CCR9 Proinflammatory cytokine Receptors CCR Crohn Disease Intestine Small medicine Immunology and Allergy Mesenteric lymph nodes Humans Immunity Mucosal Lamina propria Mucous Membrane biology Cytokine medicine.anatomical_structure Cancer research biology.protein Cytokines Female Receptors Chemokine Lymph Nodes CCL25 CC chemokine receptors |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 178(5) |
| ISSN: | 0022-1767 |
| Popis: | CCL25/CCR9 chemokine ligand/receptor pair has been reported to play an important role in small bowel (SB) immunity and inflammation. We have previously reported an aberrant SB expression of CCL25 in Crohn’s disease (CD) and an increased frequency of CCR9+ T cells in the peripheral blood of patients with SB inflammatory diseases such as CD and celiac disease. In this study, we have characterized the phenotype and effector function of CCR9+ T cells in mucosal lymphoid tissues in CD. We show that CCR9+ T cells isolated from mesenteric lymph nodes (MLN) draining CD SB express a more activated phenotype compared with MLN draining normal SB. Stimulation of CCR9+ T cells isolated from CD SB lamina propria produced more IFN-γ and IL-17 in response to anti-CD3 or IL-12/IL-18 stimulation compared with those isolated from normal SB. The addition of TL1A to the cytokine combination markedly augmented the secretion of IFN-γ, but not IL-17, by CD lamina propria CCR9+ T cells. CCL25 incubation of CD SB lamina propria lymphocytes and MLN lymphocytes increased their adhesion to VCAM-1/Fc in vitro. Finally, the TCRVβ analysis of CCR9+ T cells revealed a diverse TCRVβ repertoire among MLN CCR9+ T cells in patients with SB CD. Our data indicate that CCR9+ T cells in SB CD are proinflammatory and support the rationale for the use of CCR9 antagonists for the treatment of human SB CD. |
| Databáze: | OpenAIRE |
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