AUTHOR=Lavalette Sophie , Conart Jean-Baptiste , Touhami Sara , Roubeix Christophe , Houssier Marianne , Augustin Sébastien , Raoul William , Combadière Christophe , Febbraio Maria , Ong Huy , Chemtob Sylvain , Sahel José-Alain , Delarasse Cécile , Guillonneau Xavier , Sennlaub Florian 

TITLE=CD36 Deficiency Inhibits Retinal Inflammation and Retinal Degeneration in Cx3cr1 Knockout Mice

JOURNAL=Frontiers in Immunology

VOLUME=10

YEAR=2020

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.03032

DOI=10.3389/fimmu.2019.03032

ISSN=1664-3224

ABSTRACT=<p><bold>Background:</bold> CD36, a member of the class B scavenger receptor family, participates in Toll-like receptor signaling on mononuclear phagocytes (MP) and can promote sterile pathogenic inflammation. We here analyzed the effect of CD36 deficiency on retinal inflammation and photoreceptor degeneration, the hallmarks of age-related macular degeneration (AMD), that characterize <italic>Cx3cr1</italic><sup>−/−</sup>mice.</p><p><bold>Methods:</bold> We analyzed subretinal MP accumulation, and cone- and rod-degeneration in light-challenged and aged, CD36 competent or deficient, hyper-inflammatory <italic>Cx3cr1</italic><sup>−/−</sup> mice, using histology and immune-stained retinal flatmounts. Monocytes (Mo) were subretinally adoptively transferred to evaluate their elimination rate from the subretinal space and Interleukin 6 (IL-6) secretion from cultured Mo-derived cells (MdCs) of the different mouse strains were analyzed.</p><p><bold>Results:</bold> CD36 deficient <italic>Cx3cr1</italic><sup>−/−</sup> mice were protected against age- and light-induced subretinal inflammation and associated cone and rod degeneration. CD36 deficiency in <italic>Cx3cr1</italic><sup>−/−</sup> MPs inhibited their prolonged survival in the immune-suppressive subretinal space and reduced the exaggerated IL-6 secretion observed in <italic>Cx3cr1</italic><sup>−/−</sup> MPs that we previously showed leads to increased subretinal MP survival.</p><p><bold>Conclusion:</bold><italic>Cd36</italic> deficiency significantly protected hyperinflammatory <italic>Cx3cr1</italic><sup>−/−</sup> mice against subretinal MP accumulation and associated photoreceptor degeneration. The observed CD36-dependent induction of pro-inflammatory IL-6 might be at least partially responsible for the prolonged MP survival in the immune-suppressive environment and its pathological consequences on photoreceptor homeostasis.</p>