Plasmacytoid DCs (pDCs) have important antiviral functions due to their ability to produce vast amounts of type I interferon. In Blood, Kaisho and colleagues identify an important cell-intrinsic role for Spi-B (a member of the Ets family of transcription factors) in pDC function. Spi-B has high expression in pDCs, but so far its precise role has been unclear. In addition, the transcription factor E2-2 is known to be critical for early pDC development. The authors find that Spi-B associates and acts in synergy with the type I interferon–inducing 'master' transcription factor IRF7. Spi-B-deficient mice show a complex pattern of development, with fewer mature bone marrow pDCs, but this effect is less apparent for peripheral pDCs. However, Spi-B-deficient pDCs have impaired type I interferon responses to stimulation of TLR7 and TLR9. Transcriptional profiling suggests that Spi-B regulates a set of genes that overlaps but is distinct from those regulated by E2-2, with Spi-B being involved chiefly in the functional maturation of pDCs.

Blood 120, 4733–4743 (2012)