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* Inflammatory Bowel Disease Center and Immunobiology Institute, and
Division of Colorectal Surgery, Cedars-Sinai Medical Center and the UCLA School of Medicine, Los Angeles, CA 90048
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-
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-, 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 TCRV
analysis of CCR9+ T cells revealed a diverse TCRV 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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by grants from the Broad Medical Research Program in Inflammatory Bowel Diseases by the Eli and Edythe L. Broad Foundation (to K.A.P.).
2 M.S. and Q.T.Y. contributed equally to this work and should be considered as first authors.
3 Address correspondence and reprint requests to Dr. Konstantinos A. Papadakis, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, D-4063, Los Angeles, CA 90048. E-mail address: Papadakisk{at}cshs.org
4 Abbreviations used in this paper: CD, Crohn’s disease; HPF, high power field; IBD, inflammatory bowel disease; LP, lamina propria; LPL, lamina propria lymphocyte; MFI, mean fluorescence intensity; MLN, mesenteric lymph node; PB, peripheral blood; SB, small bowel; UC, ulcerative colitis.
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