Hemophagocytic lymphohistiocytosis (HLH) is a rare, severe genetic disease that causes dramatic, life-threatening inflammation by hyperactivation of the immune cells. The cytotoxic T lymphocyte (CTL) and natural killer (NK) cell exocytosis functions are crucial for the elimination of infected or malignant cells, which is impaired in a group of diseases like HLH. The molecular underlying mechanisms remain largely elusive. Cells from a patient suffering from this disease were analysed, revealing a mutation in the enzyme RhoG. By establishing a human RhoG-knock out cell line, it was shown that the absence of RhoG impairs the exocytosis process, thus defining the molecular pathomechanism and identifyig a yet unreported genetic form of HLH.
RhoG deficiency abrogates cytotoxicity of human lymphocytes and causes hemophagocytic lymphohistiocytosis
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