226: The transcription factor IRF8 is required for the development of basophils
Basophils are the rarest granulocytes circulating in the peripheral blood. Although their non-redundant roles in Th2-type immunity and allergic disorders have been clarified, little is known about the pathways and regulators of their development. Interferon Regulatory Factor-8 (IRF8) is a transcription factor known to promote the development of monocytes/macrophages and dendritic cells while inhibiting that of neutrophils. In this report, we show that this transcription factor is required for the development of the basophil lineage. Irf8 −/− mice display a severe reduction of basophil counts in the bone marrow, peripheral blood and spleen. Bone marrow transfer experiments showed that IRF8 functions in a bone marrow cell-intrinsic manner. Analysis of bone marrow progenitors revealed that the number of granulocyte-committed progenitors (GPs) in Irf8 −/− mice is comparable to that of wild-type mice, while that of basophil-committed progenitors (BaPs) is diminished. Using IRF8-GFP knock-in mice, we found that GPs but not BaPs and mature basophils express IRF8, suggesting that IRF8 may act in the stage of GPs. Indeed, GPs purified from Irf8 −/− mice failed to efficiently give rise to basophils in vitro in the presence of IL-3. Taken together, these results uncover a previously unrecognized role of IRF8 in granulocyte development.