CX3CL1 expression in the conjunctiva is involved in immune cell trafficking during toxic ocular surface inflammation.
Inappropriate expression of the chemokine CX3CL1 is reportedly known to act on inflammatory conditions in extraocular immune diseases. We studied the expression and effects of CX3CL1 in human patients, cultured human conjunctival cells, and transgenic mice exposed to benzalkonium chloride (BAC), a commonly used preservative in ophthalmic medications despite its proinflammatory properties, to determine whether CX3CL1 is involved in conjunctival inflammation. We report that CX3CL1 expression is increased in the conjunctiva of patients receiving BAC-containing medication, and correlates with clinical inflammation. BAC enhances the production of CX3CL1 in a conjunctival epithelial cell line, through the tumor-necrosis factor-α pathway, which attracts specific leukocyte subsets. In vivo, BAC-induced macrophage infiltration and subsequent inflammation of the conjunctiva is decreased in CX3CR1-deficient mice as compared with CX3CR1(+/+) controls. This translational study opens new avenue to investigate ocular surface disorders by focusing on chemokine-related inflammation and immune cell trafficking in the ocular conjunctival mucosa.
UPMC University Paris 6, Institut de la Vision, UMRS968, Paris, France.
A
A
Denoyer
D
D
Godefroy
I
I
Célérier
J
J
Frugier
L
L
Riancho
F
F
Baudouin
W
W
Rostène
C
C
Baudouin
D000328:Adult; D000368:Aged; D000818:Animals; D001548:Benzalkonium Compounds / Q000009:adverse effects; D000073883:CX3C Chemokine Receptor 1; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D054428:Chemokine CX3CL1 / Q000235:genetics* / Q000276:immunology; D003228:Conjunctiva / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D003231:Conjunctivitis / Q000139:chemically induced / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D011310:Preservatives, Pharmaceutical / Q000009:adverse effects; D019707:Receptors, Chemokine / Q000172:deficiency / Q000235:genetics* / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology
D001548:Benzalkonium Compounds; D000073883:CX3C Chemokine Receptor 1; D054428:Chemokine CX3CL1; C471885:Cx3cr1 protein, mouse; D011310:Preservatives, Pharmaceutical; D019707:Receptors, Chemokine; D014409:Tumor Necrosis Factor-alpha