Patrolling Murine Monocytes Are Defined by Their Expression of the Orphan Nuclear Receptor, Nur77 (nr4a1)

Abstract 4723

‘Resident’ or ‘patrolling’ monocytes have recently been described as a unique subset of myeloid cells that differ in phenotype and function from classic inflammatory monocytes. Resident monocytes are distinguished by their ‘crawling’ migration on endothelial surfaces, their immunosuppressive activity, and their unique pattern of surface protein expression: Ly6C^lo, CX3CR1^hi, CCR2^-, LFA-1+, and PDL-1⁺. Using a Nur77-eGFP reporter mouse, we show that all murine patrolling monocytes, but not conventional monocytes express Nur77⁺ (also known as NR4A1), a member of the Nur orphan nuclear receptor family that regulates cell fate decisions several cell types and inhibits leukemogenesis. Nur77 is an immediate early response gene, and we have recently determined that it is a sensitive indicator of antigen receptor signaling among T cells. We therefore propose that its expression among patrolling monocytes is an indication that these cells are actively receiving signals, perhaps via interactions with the endothelium. We are currently working to identify these signals and our preliminary data suggest that adhesion molecules play an influential role.

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