American Society of Hematology, Blood, 9(121), p. 1574-1583, 2013
DOI: 10.1182/blood-2012-07-445650
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Anti-viral immunity and cross-presentation is mediated constitutively through CD8α(+) 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 have addressed the nature of the differentiation blocks observed in the absence of these factors and found that while all four factors are required for CD103(+) DC development, only Irf8 is essential for CD8α(+) DC. CD8α(+) DCs emerged in the absence of Id2, Nfil3 and Batf3 in short-term bone marrow reconstitution. These 'induced' CD8α(+) DCs exhibit several hallmarks of classical CD8α(+) 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 CD8α(+) DCs emerge independent of Id2, Nfil3 and Batf3, but dependent on Irf8.