Sarcoidosis is an inflammatory disease that can affect any organ, with the lungs as the most common site affected. The disease is characterized by an abnormal tissue organization of immune cells which results in a granuloma. Monocytes, a subset of white blood cells, are partially responsible for sarcoidosis development and progression because of their chronic and aberrant overactivation. Mechanisms that underlie this phenomenon have been recently identified with the discovery of epigenetic modifications that are induced by the environment. The function of monocytes is therefore modified for a long-time. During sarcoidosis, we hypothesized that monocytes are overactivated as a consequence of specific epigenetic modifications. To this end, we first studied the epigenetic signature of monocytes from sarcoidosis patients, which was compared with tuberculosis patients, an infectious disease with many clinical and histological similarities to sarcoidosis, and with healthy volunteers. We were able to confirm our initial hypothesis on a maladaptive innate immune training occuring in each disease. Ongoing work aims first to extend this analysis including more patients and studying the effect of treatment on this signature. We are also running a deep immune profiling of patients suffering either from sarcoidosis or from tuberculosis.
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