Department of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America.
Yonsei University College of Medicine, Seoul, South Korea.
PLoS One. 2018 Jun 1;13(6):e0198608. doi: 10.1371/journal.pone.0198608. eCollection 2018.
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 CD45intCD11bint 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 CD45intCD11bint population (77.3%±5.9%, P = 0.03) than on CD45highCD11b+ population (14.8%±16.6%, P = 0.49). In addition, CD45intCD11bint 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 CD45highCD11b+ population. Moreover, the CD45intCD11bint 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 CD45intCD11bint cells increased early after IRI, and then abruptly decreased 48h later, whereas CD45highCD11b+ cells steadily increased after IRI before declining at 72h (P = 0.03). We also identified the CD45intCD11bint MPC subtype in human kidney. We conclude that CD45intCD11bint 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.
肾脏免疫细胞在许多疾病的发病机制中发挥着重要作用，包括缺血再灌注损伤（IRI）和移植排斥反应。在研究小鼠肾脏 T 细胞时，我们偶然发现了一种肾脏单核吞噬细胞（MPC）亚群，其特征是 CD45 和 CD11b 的表面表达中等。这些 CD45intCD11bint MPC 进一步被鉴定为 F4/80+MHCII+CX3CR1+Ly6C-细胞，占正常小鼠肾脏总 CD45+细胞的约 17%（P < 0.01），几乎不存在于除心脏以外的所有其他检查器官中。全身氯膦酸盐处理对 CD45intCD11bint 群体的耗竭作用更为显著（77.3%±5.9%，P = 0.03），而对 CD45highCD11b+群体的耗竭作用较小（14.8%±16.6%，P = 0.49）。此外，CD45intCD11bint MPC 在正常肾脏中具有更高的吞噬功能（35.6%±3.3%比 24.1%±2.2%，P = 0.04），但在缺血后肾脏中的吞噬能力较低（54.9%±1.0%比 67.8%±1.9%，P < 0.01）与 CD45highCD11b+群体相比。此外，CD45intCD11bint 群体在脂多糖（LPS）刺激后具有更高的促炎肿瘤坏死因子（TNF）-α的细胞内产生（58.4%±5.2%比 27.3%±0.9%，P < 0.001），而在肾 IRI 后产生抗炎白细胞介素（IL）-10 的水平较低（7.2%±1.3%比 14.9%±2.2%，P = 0.02），这表明在炎症条件下具有功能作用。CD45intCD11bint 细胞在 IRI 后早期增加，然后在 48 小时后突然减少，而 CD45highCD11b+细胞在 IRI 后持续增加，然后在 72 小时后下降（P = 0.03）。我们还在人类肾脏中鉴定出 CD45intCD11bint 细胞。我们得出结论，CD45intCD11bint F4/80+MHCII+CX3CR1+Ly6C-群体代表了在小鼠和人类肾脏中均发现的独特 MPC 亚群。未来的研究将进一步表征它们在肾脏健康和疾病中的作用。
