Characterization of kidney CD45(int)CD11b(int)F4/80(+)MHCII(+)CX3CR1(+)Ly6C(-) “intermediate mononuclear phagocytic cells”

Kidney immune cells play important roles in pathogenesis of many diseases, including ischemia-reperfusion injury (IRI) and transplant rejection. While studying murine kidney T cells, we serendipitously identified a kidney mononuclear phagocytic cell (MPC) subset characterized by intermediate surface expression of CD45 and CD11b. These CD45(int)CD11b(int) MPCs were further identified as F4/80(+)MHCII(+)CX3CR1(+)Ly6C(-) cells, comprising ~17% of total CD45(+) cells in normal mouse kidney (P < 0.01) and virtually absent from all other organs examined except the heart. Systemic clodronate treatment had more significant depletive effect on the CD45(int)CD11b(int) population (77.3%±5.9%, P = 0.03) than on CD45(high)CD11b(+) population (14.8%±16.6%, P = 0.49). In addition, CD45(int)CD11b(int) MPCs had higher phagocytic function in the normal kidney (35.6%±3.3% vs. 24.1%±2.2%, P = 0.04), but lower phagocytic capacity in post-ischemic kidney (54.9%±1.0% vs. 67.8%±1.9%, P < 0.01) compared to the CD45(high)CD11b(+) population. Moreover, the CD45(int)CD11b(int) population had higher intracellular production of the pro-inflammatory tumor necrosis factor (TNF)-α (58.4%±5.2% vs. 27.3%±0.9%, P < 0.001) after lipopolysaccharide (LPS) stimulation and lower production of the anti-inflammatory interleukin (IL)-10 (7.2%±1.3% vs. 14.9%±2.2%, P = 0.02) following kidney IRI, suggesting a functional role under inflammatory conditions. The CD45(int)CD11b(int) cells increased early after IRI, and then abruptly decreased 48h later, whereas CD45(high)CD11b(+) cells steadily increased after IRI before declining at 72h (P = 0.03). We also identified the CD45(int)CD11b(int) MPC subtype in human kidney. We conclude that CD45(int)CD11b(int) F4/80(+)MHCII(+)CX3CR1(+)Ly6C(-)population represent a unique subset of MPCs found in both mouse and human kidneys. Future studies will further characterize their role in kidney health and disease.