Innate and adaptive immunity against oxidative damage cooperate in the pathogenesis of age-related macular degeneration (P3367)

• Published in: The Journal of immunology (1950) Vol. 190; no. 1_Supplement; pp. 202 - 202.6
• Main Authors: Cruz-Guilloty, Fernando, Saeed, Ali, Duffort, Stephanie, Ballmick, Asha, Tan, Yaohong, Salomon, Robert, Perez, Victor
• Format: Journal Article
• Language: English
• Published: 01.05.2013
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.190.Supp.202.6

Abstract While our knowledge of acute immune responses is extensive, the cooperation of innate and adaptive immunity in chronic inflammatory diseases remains poorly defined. Age-related macular degeneration (AMD) is the leading cause of legal blindness in the developed world. Recently, the immune system has been shown to play a role in AMD. However, the specific roles of the adaptive immune system and different types of macrophages have not been studied in detail. Oxidative stress is a major contributing factor in the development of pathological inflammatory conditions, including atherosclerosis and AMD. Carboxyethylpyrrole (CEP) is a lipid peroxidation product associated with AMD and mice immunized with CEP-adducted self proteins develop AMD-like pathology. Here, we show CEP-specific T cell activation, pro-inflammatory cytokine production (IFN- γ, IL-17) and infiltration of M1 macrophages in the subretinal space, linking both the adaptive and innate immune systems in the onset of AMD. In vitro, CEP-specific T cells specifically promote M1 macrophage differentiation, while CEP directly induces TLR-2-independent M1 polarization. Moreover, CEP-immunized Ccr2-deficient mice lack macrophage infiltration and retinal lesions, suggesting a deleterious role for macrophages in this model. Our data provide new insights into the pathogenesis and possible treatment of AMD, while providing a more general view of chronic inflammation applicable to other settings.