Unbiased profiling of the hemophagocytic lymphohistiocytic syndrome by high-throughput single-cell transcriptomic analysis
INSERM DR Paris 5
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The understanding of the molecular and cellular events leading to the occurrence of HLH is critical for the design of more efficient therapies to treat this otherwise life-threatening syndrome. Genetic studies of several HLH patients have contributed to our understanding of the link between the genetic defects of the cytotoxic machinery and the aberrant immune balance characterizing this severe condition. However, even if the link between impaired cytotoxicity and HLH development has been clearly established, other genetic forms of HLH present without detectable defects in lymphocytes’ cytotoxicity, indicating that defects in other regulatory mechanism(s) could contribute to HLH development in these conditions. Our project intends to unveil new immunoregulatory mechanism(s) critical to maintain immune homeostasis. To address this question, we intend to dissect the complexity of immune regulatory networks in an unbiased way by performing transcriptional analysis at the single cell level. The successful accomplishment of our project will allow the identification of particular transcriptomic signatures characterizing well-known and until now undescribed forms of HLH, opening new paths for improving diagnosis and patient treatment by developing new therapies. Therefore, this proposal represents a major step towards a more personalized medicine for patients affected by this devastating condition.