CCL25/CCR9 promotes the induction and function of CD103 on intestinal intraepithelial lymphocytes.
The integrin CD103 and the chemokine receptor CCR9 are co-expressed on small intestinal CD8(+) intraepithelial lymphocytes (IEL), naïve murine CD8(+) T cells and by a small population of effector/memory CD8(+) T cells, indicating a potential role for CCR9 in regulating CD103 expression and function. Here, we demonstrate that CD103, in contrast to CCR9, is down-regulated on CD8(+) T cells following their activation in mesenteric lymph nodes and that effector CD8(+) T cells upon initial entry into the small intestinal epithelium are CCR9(+)CD103(-). CD103 was rapidly induced on wild-type CD8(+) T cells subsequent to their entry into the small intestinal epithelium, however, CCR9(-/-) CD8(+) T cells exhibited a significant delay in CD103 induction at this site. In addition, the CCR9 ligand, CCL25, that is constitutively expressed in the small intestinal epithelium, induced transient, dose-dependent and pertussis toxin-sensitive CD103-mediated adhesion of CD8(+) small intestinal IEL to a murine E-cadherin human Fc (mEFc) fusion protein. Together, these results demonstrate a role for CCR9/CCL25 in promoting the induction and function of CD103 on CD8(+) IEL and suggest that this chemokine receptor/chemokine pair may function to regulate lymphocyte-epithelial interactions in the small intestinal mucosa.
Ericsson
Anna
A
Immunology Section, Department of Cell and Molecular Biology, Lund University, Lund, Sweden.
Svensson
Marcus
M
Arya
Anu
A
Agace
William W
WW
D019264:Adoptive Transfer; D000818:Animals; D015703:Antigens, CD / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D019742:Chemokines, CC / Q000276:immunology* / Q000378:metabolism; D015536:Down-Regulation; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000378:metabolism; D039001:Integrin alpha Chains / Q000276:immunology* / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D054388:Receptors, CCR; D019707:Receptors, Chemokine / Q000276:immunology* / Q000378:metabolism
D015703:Antigens, CD; C119309:CC chemokine receptor 9; D015820:Cadherins; C491541:Ccl25 protein, mouse; D019742:Chemokines, CC; D007141:Immunoglobulin Fc Fragments; D039001:Integrin alpha Chains; D054388:Receptors, CCR; D019707:Receptors, Chemokine; C091367:alpha E integrins