It has recently been suggested that C-C chemokines may play a role in the organ-specific homing of lymphocytes, but there is not enough in vivo evidence in intestinal mucosa. The aim of this study was to examine whether thymus-expressed chemokine (TECK)/CCL25 and its ligand CCR9 are involved in T-lymphocyte interaction with microvessels of murine intestinal mucosa. T lymphocytes from the small intestine were fluorescence labeled, and their adhesion to mucosal microvessels was observed by intravital microscopy. Lamina proprial lymphocytes (LPL) and intraepithelial lymphocytes (IEL) adhered to both the small intestine and colon, and desensitization of CCR9 with TECK/CCL25 or anti-TECK/CCL25 antibody significantly inhibited these adhesions only in small intestine. At both sites, TNF-α significantly increased LPL adhesion but not IEL adhesion. Desensitization of CCR9 or anti-TECK/CCL25 antibody also attenuated the TNF-α-induced LPL adhesion in the small intestine. Increased expression of TECK/CCL25 by TNF-α was observed in the lamina propria of small intestine. TECK/CCL25 may thus play an important role in the adherence of mucosal lymphocytes to the microvessels of the small intestine but not the colon under uninflamed as well as inflamed conditions.

T-lymphocyte adherence to microvessels of the small intestinal mucosa was significantly enhanced after butter ingestion. This enhancement is due to increase in expression levels of adhesion molecules of the intestinal mucosa, which is mediated by TNF-alpha from macrophages in the intestinal lamina propria.

The results show that CD-DST is capable of selecting the responders and the respective optimal regimens, and also delineating the patients less likely benefit from treatment.

Objective: Although it is known that the chemokines CXCL12 and CCL20 are expressed in the intestine, their contribution to lymphocyte homing has not been investigated in detail. The authors investigated whether the CXCL12‐CXCR4 and CCL20‐CCR6 systems are involved in T lymphocyte–endothelial interaction in microvessels of the small and large intestines. Methods: Labeled lamina proprial lymphocytes (LPLs) were administered to mice, and their adhesion to microvessels of normal and TNF‐α –induced inflamed intestinal mucosa was observed under an intravital microscope. Antibodies against CXCL12, CCL‐20, or CCL‐25 were administered prior to lymphocyte administration, and in some experiments CXCR4 or CCR6 on LPLs was desensitized with an excess amount of chemokine. Results: LPLs adhered to microvessels of the ileum and colon, and TNF‐α induced a significant accumulation at both sites. Blocking of the CXCL12‐CXCR4 system significantly inhibited the LPL adhesion in the ileum and colon under both normal and TNF‐α –treated conditions. However, blocking of the CCL20‐CCR6 system significantly attenuated LPL adhesion only under a TNF‐α –treated condition. There was an additive inhibitory effect on LPL adherence by CXCL12 and CCL20 blocking in TNF‐α –induced inflamed intestines. There was also an additive function of the CCL25‐CCR9 system in LPL accumulation in the small intestine. Conclusion: Several chemokine systems may play significant roles cooperatively in vivo in LPL adherence to microvessels of intestinal mucosa.

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