The BXH2 mutation in IRF8 differentially impairs dendritic cell subset development in the mouse.

ABSTRACT: Among dendritic cell (DC) subsets, CD8alpha(+) DCs and plasmacytoid DCs (pDCs) produce high levels of IL12 and type I interferons (IFNs), respectively, and confer early innate immunity. Development of CD8alpha(+) DCs and pDCs requires the interferon regulatory factor 8 (IRF8). Recently, a spontaneous point mutation was identified in the Irf8/Icsbp gene in the BXH2 mouse, which exhibits an immunodeficient phenotype similar to the IRF8 knockout (KO) mouse. We show that this mutation, designated IRF8(R294C), abolishes the development of CD8alpha(+) DCs without impairing pDC development, and eliminates production of IL12p40, while retaining that of type I IFNs. Electrophoretic mobility shift and chromatin immunoprecipitation assays indicated that IRF8(R294C) failed to interact with partner tra

SUBMITTER: Tailor P 

PROVIDER: S-EPMC2234043 | biostudies-literature | 2008 Feb

REPOSITORIES: biostudies-literature