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Barbara P. Vistica, Vanessa Montalvo-Reddin, Guangpu Shi, Lindsey Nugent, Laura Quigley, Daniel W. McVicar, Igal Gery; DAP-12, a Major Immunomediator, Either Promotes or Suppresses EAU Development. Invest. Ophthalmol. Vis. Sci. 2012;53(14):6239.
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DAP12 (DNAX-activating protein of 12kDa), a transmembrane signaling molecule, plays a major role in the immune response by transducing a variety of activation signals from receptors on antigen-presenting and other leukocytes. The role of DAP12 in the etiology of pathogenic autoimmunity has been controversial, since DAP12 deficient mice reportedly exhibit either enhanced or depressed experimental autoimmune diseases. Here, we compared DAP12 deficient mice and wild type (WT) controls for their susceptibility to EAU induction and immune responsiveness to the uveitogenic antigen
DAP12 deficient mice and their C57Bl/6 WT controls were obtained from two animal facilities, on the same campus, both specific pathogen free (SPF) but with different standards for helicobacter and other organisms. The mice were immunized with interphotoreceptor retinoid-binding protein (IRBP) and their development of EAU was evaluated by fundoscopy and histological examination. Lymphoid cells from draining lymph nodes were cultured with IRBP to measure proliferation and cytokine release.
Although disease in control mice from both facilities was comparable DAP12 deficient mice from the SPF facility with less stringent health standards were superior to their WT controls in both the severity of their ocular inflammation and the levels of proliferation and of IL-17 and interferon gamma produced by their lymphocytes. In contrast, DAP12 deficient mice from the cleaner rodent barrier facility were inferior to their controls by both parameters.
Our data provide a possible resolution to the controversy concerning the role of DAP12 in the induction of EAU: deficiency in this molecule can either promote or suppress the pathogenic response, even when the same experimental system is used. The difference we observed between the two portions of the study could be attributed only to conditions within the animal facilities that shape the immune systems.
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