Characterization of Nur77+ Cells in Murine Peripheral Blood.

Abstract 1361

Poster Board I-385

The expression of Nur77/NR4A1, one member of the Nur Orphan Nuclear Receptor family, is tightly regulated in many cell types, including myeloid and lymphoid lineages, and can change rapidly in response to a variety of external stimuli. Best known for its role in regulating apoptosis by either transcribing lethal genes or by initiating mitochondrial production of cytochrome c, Nur77 may also play other non-apoptotic roles. In an effort to understand the fate and function of cells that upregulate Nur77, we developed a transgenic Nur77-eGFP reporter mouse. Our analysis of cells in the peripheral blood of these mice reveals two populations of circulating cells that express GFP (Nur77) ‘constitutively’: T lymphocytes and a subset of monocytes. Our preliminary data suggest that the GFP+ T cells, which, interestingly are enriched for regulatory T cells, are recent thymic emigrants that have upregulated Nur77 as a consequence of TCR stimulation during maturation. Our observations also indicate that the GFP+ monocytes define a subpopulation of ‘patrolling’ cells that may ultimately differentiate into splenic dendritic cells. Understanding the identity of these circulating GFP+ cells should provide us with insights into the regulation and function of Nur77 itself. The analysis may also clarify the significance of phenotypic differences among blood cell subtypes by providing additional information about cell origin and activity.

We thank the Arnold and Mabel Beckman Foundation (HH), HHMI (TB), and NSF (#MCB-0744570 (JP and NC)) for their support for this work.