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The Tyro3, Axl and Mertk (TAM) triply knockout (TKO) mice exhibit systemic autoimmune diseases, with characteristics of increased proinflammatory cytokine production, autoantibody deposition and autoreactive lymphocyte infiltration into a variety of tissues. Here we show that TKO mice produce high level of serum TNF-α and specific autoantibodies deposited onto brain blood vessels. The brain-blood barrier (BBB) in mutant brains exhibited increased permeability for Evans blue and fluorescent-dextran, suggesting a breakdown of the BBB in the mutant brains. Impaired BBB integrity facilitated autoreactive T cells infiltrating into all regions of the mutant brains. Brain autoimmune disorder caused accumulation of the ubiquitin-reactive aggregates in the mutant hippocampus, and early formation of autofluorescent lipofuscins in the neurons throughout the entire brains. Chronic neuroinflammation caused damage of the hippocampal mossy fibers and neuronal apoptotic death. This study shows that chronic systemic inflammation and autoimmune disorders in the TKO mice cause neuronal damage and death. [ABSTRACT FROM AUTHOR]

Highlights: [•] Pulmonary fibrosis is a common disease with no effective treatment. [•] Bleomycin induced pulmonary fibrosis is the most common animal model for studying pulmonary fibrosis. [•] Neuroepithelial bodies (NEBs) increase in many pulmonary diseases related to lung injury. However, the relation between NEBs and pulmonary fibrosis is not known. [•] We found bleomycin treatment increases the number and size of NEBs. This may reveal a new mechanism for the disease. [ABSTRACT FROM AUTHOR]