Immunology

Diversity in Phenotype and Steroid Hormone Dependence in Dendritic Cells and Macrophages in the Mouse Uterus

Abstract
The dendritic cells and related antigen presenting cells (APCs) that activate lymphocytes for acquired immunity in the female reproductive tract are not well characterised. The aim of this study was to examine heterogeneity amongst uterine APCs in mice and specifically to determine whether phenotypically and functionally distinct subpopulations of dendritic cells and macrophages can be identified. Using immunohistochemistry, abundant cells expressing APC-restricted molecules MHC class II, F4/80, class A scavenger receptor, macrosialin and sialoadhesin were evident in estrous mice. Cells expressing the costimulatory molecule B7-2 were rarely observed. Flow cytometric analysis revealed three sub-populations of uterine APCs. Undifferentiated macrophages were F4/80+MHC class II- cells, of which 70-80 % expressed CD11b, but few expressed class A scavenger receptor, macrosialin or sialoadhesin. Mature macrophages were F4/80+MHC class II+ cells of which approximately 50% expressed CD11b, class A scavenger receptor, macrosialin and sialoadhesin. Uterine dendritic cells were F4/80-MHC class II+ cells with stimulatory immunoaccessory function relative to uterine macrophages, and heterogenous expression of dendritic markers 33D1, DEC205, CD11c and CD1. Experiments in ovariectomised mice showed that immature macrophages were steroid-hormone dependent but that mature macrophages and dendritic cells persist after depletion of ovarian steroid hormones, although with altered phenotypes. In summary, our findings identify three discrete populations of APCs inhabiting the murine uterus, and suggest that both mature macrophages and dendritic cells differentiate from immature macrophage precursor cells. Plasticity in the ontogenetic and functional relationships between uterine dendritic cells and macrophages is likely to be critical in regulating immune responses conducive to reproductive success.

Key words: Female Reproductive Tract • Immunology • Steroid hormones • Uterus

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