Myeloid Inhibitory C-type lectin-like receptor (MICL, CLEC12A) – a central regulator of immunity

My group recently discovered that functional loss of the inhibitory C-type lectin receptor MICL on neutrophils, through either genetic deletion or in the presence of autoantibodies, leads to inflammatory pathology that exacerbates autoimmune diseases. In contrast, loss of MICL function was protective against invasive fungal infections. I will capitalize on these important discoveries to generate fundamental new insights into the physiological functions of MICL in non-infectious and infectious disease pathogenesis. This will be achieved through the following Aims: (1) To elucidate MICL functions on myeloid cells.These studies will provide crucial information revealing the cellular roles, functions and underlying mechanisms by which MICL regulates immunity.(2) To investigate the role of anti-MICL autoantibodies in autoimmune disease pathology.These analyses will reveal the underlying mechanisms by which anti-MICL autoantibodies mediate their pathological effects and develop approaches to block the effect of these autoantibodies during disease. (3) To define the role of MICL during fungal infections.These experiments will ascertain the role of MICL during fungal infections and explore mechanisms to beneficially modulate this receptor’s function. In sum, this research will reveal the mechanisms underlying the functions of an essential immune regulator; discoveries that will have direct therapeutic implications.