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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Animals, Apoptosis, Diabetes Mellitus, Type 1, Female, Interferon-alpha, Interferon-beta, Interferon-gamma, Interleukin-12, Janus Kinase 2, Lipopolysaccharides, Macrophages, Mice, Mice, Inbred C57BL, Mice, Inbred NOD, Phosphorylation, Receptor, Interferon alpha-beta, Receptors, Interferon, STAT1 Transcription Factor, Signal Transduction, Tumor Necrosis Factor-alpha.
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Do macrophages from nonobese diabetic mouse have a selective defect in IFN-γ but not IFN-α/β receptor pathway? Context: Aberrant regulation of innate immune cells such as macrophages has been implicated in the onset and progression of type 1 diabetes (T1D). Macrophages from nonobese diabetic (NOD) mouse, an animal model of T1D, entail developmental and functional defects that are often associated with hypo-responsiveness to interferon (IFN)-γ. We aimed to uncover a mechanism underlying this phenomenon. We analyzed the receptor pathway along with the response of macrophages exposed to IFN-γ and the related IFNs such as IFN-α/β. We found that NOD macrophages failed to fully respond to IFN-γ but not to IFN-α for the production of inflammatory cytokines (e.g. TNF-α and IL-12). NOD macrophages were also resistant to apoptotic pathway induced by IFN-γ and LPS. Analyses of receptor pathway revealed that STAT1 pathway of intracellular signaling was selectively impaired in NOD macrophages exposed to IFN-γ but not to IFN-α/β. Further, these defects correlated with a low phosphorylation level of JAK2, and were related to impaired up-regulation of surface IFN-γ receptor 2 (IFN-γR2) by IFN-γ.
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Taken together, our results suggest that NOD macrophages have a selective defect in IFN-γ but not IFN-α/β receptor pathway. As IFN-γ and IFN-α have been implicated in the development of autoimmunity towards β-cells, such an unanticipated selectivity in IFN responsiveness may provide a new insight into the pathogenesis of T1D. Final Decision: yes