Insights from Patients with Dendritic Cell Immunodeficiency.

Abstract Dendritic Cells (DCs), derived from haematopoietic stem cells, are critical to the dynamic and balanced functioning of the intact immune system and are of great interest as vehicles of immunotherapy. Genetically modified mouse models have proved powerful tools to map DC development and function in vivo but human studies have previously relied heavily on in vitro systems. Human dendritic cell immunodeficiency, resulting from single gene mutations, offers new opportunities to dissect the role of human DCs in vivo, determine the genetic requirements for their development and map their haematopoietic differentiation pathways. This review will summarise the clinical phenotypes of mutations in GATA2, IRF8 and IKZF1 genes which result in global or subset specific dendritic cell deficiencies, discuss the functional consequences of these cytopenias and how these syndromes have informed our knowledge of DC differentiation and human haematopoiesis.