Dectin-1 binding to annexins on apoptotic cells induces peripheral immune tolerance via NADPH oxidase-2

Summary Uptake of apoptotic cells (ACs) by dendritic cells (DCs) and induction of a tolerogenic DC phenotype is an important mechanism for establishing peripheral tolerance to self-antigens. The receptors involved and underlying signaling pathways are not fully understood. Here, we identify Dectin-1 as a crucial tolerogenic receptor binding with nanomolar affinity to the core domain of several annexins (annexin A1, A5, and A13) exposed on ACs. Annexins bind to Dectin-1 on a site distinct from the interaction site of pathogen-derived β-glucans. Subsequent tolerogenic signaling induces selective phosphorylation of spleen tyrosine kinase (SYK), causing activation of NADPH oxidase-2 and moderate production of reactive oxygen species. Thus, mice deficient for Dectin-1 develop autoimmune pathologies (autoantibodies and splenomegaly) and generate stronger immune responses (cytotoxic T cells) against ACs. Our data describe an important immunological checkpoint system and provide a link between immunosuppressive signals of ACs and maintenance of peripheral immune tolerance

LEARNING FROM ERRORS IN RADIOLOGY. A KOMPREHENSIVE REVIEW

Interpretation of radiological examinations in routine everyday practice, everywhere, not just in Kosovo, contains many errors and discrepancies. Fortunately, most of them are low-level errors, or if they are serious, they are mostly found and corrected in a timely manner; obviously, diagnostic errors become critical when misinterpretation or misidentification can significantly delay medical or surgical treatments. Errors can be summarized into three main categories: observation errors, errors in interpretation, and failure to suggest additional appropriate diagnostic procedures. The possibility of misdiagnosis / misinterpretation is increased even in radiologists with experience during work in emergency units and in radiologists that are at the beginning of their professional careers and in particular during residency training. Pathologies that most often constitute neuroradiology pitfalls include calcification, pseudofractures (fake fractures) , expansion of either subarachnoid or epidural space, ventricular system abnormalities, vascular system abnormalities, intracranial lesions or pseudolesions (fake lesions), and in particular neuroradiological emergencies. In order to minimize the possibility of errors, it is important to be aware of various imaging presentations of a certain pathology, to obtin clinical data, to be familiarized with and to apply the latest practical guidelines, to review post-interpretation examinations , to instruct the patient to undergo appropriate additional examination, and finally, to interpret and to communicate important pathological findings properly and at the right to the other members of treatment team