CD8α+ DCs can be induced in the absence of transcription factors Id2, Nfil3, and Batf3

Antiviral immunity and cross-presentation is mediated constitutively through CD8 alpha(+) and CD103(+) DCs. Development of these DC subsets is thought to require the transcription factors Irf8, Id2, Nfil3, and Batf3, although how this network is regulated is poorly defined. We addressed the nature of the differentiation blocks observed in the absence of these factors and found that although all 4 factors are required for CD103(+) DC development, only Irf8 is essential for CD8 alpha(+) DCs. CD8 alpha(+) DCs emerged in the absence of Id2, Nfil3 and Batf3 in short-term bone marrow reconstitution. These "induced" CD8 alpha(+) DCs exhibit several hallmarks of classic CD8 alpha(+) DCs including the expression of CD24, Tlr3, Xcr1, Clec9A, and the capacity to cross-present soluble, cell-associated antigens and viral antigens even in the absence of Batf3. Collectively, these results uncover a previously undescribed pathway by which CD8 alpha(+) DCs emerge independent of Id2, Nfil3, and Batf3, but dependent on Irf8.