Reduced chemokine receptor 9 on intraepithelial lymphocytes in celiac disease suggests persistent epithelial activation.
OBJECTIVE
Celiac disease is caused by an inappropriate immune response to dietary gluten, with increased epithelial lymphocyte infiltration in the duodenum/jejunum as a hallmark. The chemokine receptor 9 (CCR9) is a small intestinal homing receptor normally found on most mucosal T cells in this organ. Because CCR9 expression appears to be activation dependent, we examined CCR9 on duodenal T cells from untreated and treated (gluten-free diet) patients with celiac disease and healthy controls.


METHODS
Duodenal biopsy specimens and blood samples were obtained for histologic analysis and flow-cytometric CCR9 analysis of isolated lymphocytes. CCR9 expression after activation was studied in peripheral blood T cells from healthy volunteers.


RESULTS
The median number of CCR9(+) cells among CD3(+) T cells in epithelium and lamina propria, respectively, was 56% and 48% in controls, 11% and 40% in treated patients, and 1% and 8% in untreated patients. Significant differences occurred between controls and treated or untreated patients in the epithelium but only between controls and untreated patients in the lamina propria (P=.008, all comparisons). No such differences were seen in peripheral blood, but stimulation with phorbol myristate acetate and ionomycin and, to a lesser extent, stimulation via NKG2D reduced the CCR9 expression on blood T cells.


CONCLUSIONS
CCR9 expression is reduced on epithelial and lamina propria T cells in untreated celiac disease. Down-regulation of CCR9 persists in intraepithelial T cells from well-treated patients. This suggests ongoing immune activation preferentially within the epithelium.
Olaussen
Richard W
RW
Laboratory for Immunohistochemistry and Immunopathology, Institute of Pathology, University of Oslo, Oslo, Norway. richard.olaussen@ahus.no
Karlsson
Malin R
MR
Lundin
Knut E A
KE
Jahnsen
Jørgen
J
Brandtzaeg
Per
P
Farstad
Inger N
IN
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002446:Celiac Disease / Q000097:blood / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D016207:Cytokines / Q000494:pharmacology; D015536:Down-Regulation; D004386:Duodenum / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D015759:Ionomycin / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D054388:Receptors, CCR; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000276:immunology; D055607:Receptors, Natural Killer Cell; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000911:Antibodies, Monoclonal; C119309:CC chemokine receptor 9; D016207:Cytokines; C527085:KLRK1 protein, human; D008070:Lipopolysaccharides; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011948:Receptors, Antigen, T-Cell; D054388:Receptors, CCR; D019707:Receptors, Chemokine; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D015759:Ionomycin; D013755:Tetradecanoylphorbol Acetate