Epithelial CXCR3-B regulates chemokines bioavailability in normal, but not in Sjogren's syndrome, salivary glands.
Expression of CXCR3-targeting chemokines have been demonstrated in several diseases, suggesting a critical role for CXCR3 in recruiting activated T cells to sites of immune-mediated inflammation. Sjögren's syndrome (SS) is an autoimmune disease characterized by a mononuclear cell infiltrate of activated T cells around the duct in the salivary gland. Analysis of minor salivary gland biopsy specimens from 20 healthy subjects and 18 patients with primary SS demonstrated that CXCR3, in particular, the B form of this receptor, is constitutively expressed by human salivary gland epithelial cells. Salivary gland epithelial cell cultures demonstrated that CXCR3 participate in removing relevant amount of agonists from the supernatant of exposed cells without mediating calcium flux or chemotaxis while retaining the ability to undergo internalization. Although in normal salivary gland epithelial cells, CXCR3 behaves as a chemokine-scavenging receptor, its role in SS cells is functionally impaired. The impairment of this scavenging function might favor chemotaxis, leading to heightened immigration of CXCR3-positive T lymphocytes. These findings suggest that epithelial CXCR3 may be involved in postsecretion regulation of chemokine bioavailability. They also support a critical role for CXCR3 in the pathogenesis of SS and identify its agonists as potential therapeutic targets.
Sfriso
Paolo
P
Department of Clinical and Experimental Medicine, Section of Rheumatology, Centro di Eccellenza per la Ricerca Biomedica, Padova, Italy.
Oliviero
Francesca
F
Calabrese
Fiorella
F
Miorin
Marta
M
Facco
Monica
M
Contri
Antonella
A
Cabrelle
Anna
A
Baesso
Ilenia
I
Cozzi
Franco
F
Andretta
Marilisa
M
Cassatella
Marco Antonio
MA
Fiocco
Ugo
U
Todesco
Silvano
S
Konttinen
Yrjö T
YT
Punzi
Leonardo
L
Agostini
Carlo
C
D000328:Adult; D000368:Aged; D001682:Biological Availability; D002478:Cells, Cultured; D054357:Chemokine CXCL10; D018925:Chemokines / Q000378:metabolism*; D019743:Chemokines, CXC / Q000378:metabolism; D002633:Chemotaxis; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D005260:Female; D006801:Humans; D008024:Ligands; D008875:Middle Aged; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000819:agonists / Q000378:metabolism*; D012469:Salivary Glands / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D012859:Sjogren's Syndrome / Q000276:immunology / Q000378:metabolism*
C114753:CXCL10 protein, human; C515187:CXCR3 protein, human; D054357:Chemokine CXCL10; D018925:Chemokines; D019743:Chemokines, CXC; D008024:Ligands; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine