Surprising new roles for PU.1 in the adaptive immune response

The ETS family transcription factor PU.1 is one of the best-studied regulators of hematopoiesis. While research over the past two decades has established that PU.1 is essential for many aspects of lymphoid and myeloid cell development, the more recent development of the tools that enable PU.1 function to be assessed in adult mice and in specific cell lineages has led to the discovery of some surprising new roles of this versatile factor in the adaptive immune response. Despite being required for fetal lymphopoiesis, PU.1 is dispensable for the differentiation of committed B cells. There is, however, an emerging and still uncharacterized function of PU.1 as a repressor for late B-cell differentiation. In contrast, PU.1 is required at every point for the differentiation of all dendritic cells, in part, although its regulation of the crucial receptor Flt3. Within the T-cell lineage, PU.1 is required for the earliest thymic development, although the mechanism remains unknown, while recent studies have shown a previously unknown function of PU.1 in peripheral T-cell differentiation. Here, we review insights derived from these mouse models of PU.1 deficiency, with particular emphasis on these functions of PU.1 in the lymphocyte and dendritic cell lineages.