7 research outputs found

    Religions in Vienna in the Past, Present and Future - Key Findings from the WIREL Project

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    The role of religion is currently a topic of considerable public interest in Vienna as well as across Europe. Over the course of the last half-century, Vienna has witnessed rapidly changing religious composition accompanied by consistently increasing religious diversity. The various aspects of research conducted by WIREL facilitate the global assessment of both quantitative and qualitative aspects of religious diversity in Vienna. A short report – Religions in Vienna in the Past, Present and Future –summarises the research findings with the aim of making the trends, drivers, and socio-demographic consequences of the changing religious landscape of Vienna more accessible and understandable

    Nature Communications / Human DEF6 deficiency underlies an immunodeficiency syndrome with systemic autoimmunity and aberrant CTLA-4 homeostasis

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    Immune responses need to be controlled tightly to prevent autoimmune diseases, yet underlying molecular mechanisms remain partially understood. Here, we identify biallelic mutations in three patients from two unrelated families in differentially expressed in FDCP6 homolog (DEF6) as the molecular cause of an inborn error of immunity with systemic autoimmunity. Patient T cells exhibit impaired regulation of CTLA-4 surface trafficking associated with reduced functional CTLA-4 availability, which is replicated in DEF6-knockout Jurkat cells. Mechanistically, we identify the small GTPase RAB11 as an interactor of the guanine nucleotide exchange factor DEF6, and find disrupted binding of mutant DEF6 to RAB11 as well as reduced RAB11CTLA-4 vesicles in DEF6-mutated cells. One of the patients has been treated with CTLA-4-Ig and achieved sustained remission. Collectively, we uncover DEF6 as player in immune homeostasis ensuring availability of the checkpoint protein CTLA-4 at T-cell surface, identifying a potential target for autoimmune and/or cancer therapy.(VLID)492061
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