The monocyte chemokine receptor CX3CR1 does not play a significant role in the pathogenesis of experimental autoimmune uveoretinitis.
OBJECTIVE
To examine the role of the monocyte chemokine receptor CX(3)CR1 in experimental autoimmune uveoretinitis (EAU).


METHODS
EAU was induced in naive WT, Cx(3)cr1(gfp/+), and Cx(3)cr1(gfp/gfp) C57Bl/6 mice or chimeric mice. Ocular disease severity was graded by histologic analysis of resin sections. In addition, immunohistochemistry and confocal microscopy were performed on retinal whole mounts to characterize the monocytic infiltrate and changes in retinal microglia. To determine the relative roles of resident and blood-borne monocyte-derived cells in the active phase of uveoretinitis, EAU was induced 4 weeks after transplantation in chimeric mice (Cx(3)cr1(gfp/gfp)→WT and Cx(3)cr1(gfp/+)→WT), and analysis was performed at days 14, 16, 21, and 28 after immunization.


RESULTS
After EAU induction, disease scores were not significantly different in WT, Cx(3)cr1(gfp/+), and Cx(3)cr1(gfp/gfp) mice. Chimeric studies revealed both donor- and host-derived monocyte-derived cells in the inner retinal layers during early EAU; however, it was donor monocytic cells that infiltrated the photoreceptors, the site of the target antigen. The absence of CX(3)CR1 did not impede the ability of monocyte-derived cells from Cx(3)cr1(gfp/gfp) donor mice to infiltrate during the peak of EAU.


CONCLUSIONS
The lack of CX(3)CR1 on monocyte-derived cells does not significantly influence the onset or severity of EAU. In addition, chimeric studies revealed that it is primarily blood-derived monocytes that mediate photoreceptor damage in the effector phase of EAU, and this process is not CX(3)CR1 dependent.
Kezic
Jelena
J
Centre for Ophthalmology and Visual Sciences, Lions Eye Institute, The University of Western Australia, Perth, Australia.
McMenamin
Paul G
PG
D000818:Animals; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D000073883:CX3C Chemokine Receptor 1; D002678:Chimera; D004195:Disease Models, Animal; D005136:Eye Proteins; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000473:pathology; D018613:Microscopy, Confocal; D009000:Monocytes / Q000276:immunology*; D019707:Receptors, Chemokine / Q000502:physiology*; D012173:Retinitis / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D012177:Retinol-Binding Proteins; D015866:Uveitis, Posterior / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D000099214:Retinol-Binding Proteins, Interstitial
D000073883:CX3C Chemokine Receptor 1; D005136:Eye Proteins; D019707:Receptors, Chemokine; D012177:Retinol-Binding Proteins; D000099214:Retinol-Binding Proteins, Interstitial; C471885:Cx3cr1 protein, mouse