Saito Yoichi, Fujiwara Yukio, Yamaguchi Yasuka L, Tanaka Satomi S, Miura Kyoko, Hizukuri Yoshiyuki, Yamashiro Kyoko, Hayashi Yasuhiro, Nakashima Yuta, Komohara Yoshihiro
Laboratory of Bioengineering, Faculty of Advanced Science and Technology, Kumamoto University, Kumamoto, Japan.
Department of Cell Pathology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
Dev Dyn. 2025 May 12. doi: 10.1002/dvdy.70036.
CD163 is a scavenger receptor predominantly expressed on the surfaces of macrophages in various mammalian species and is a marker of anti-inflammatory (M2-like) macrophages. High density of CD163-positive tumor-associated macrophages (TAMs) is associated with worse prognosis in various patient tumors. Interestingly, studies on mice have shown that CD163-positive TAMs only infiltrate the margins of tumor tissues, not the center. Based on these observations, we hypothesized that circulating monocyte-derived macrophages (MDMs), which are the origin of most TAMs, do not express CD163 in mice.
We examined CD163 expression in MDMs, differentiated from healthy animals in vitro, and in normal, pathogenic, and tumorigenic macrophages infiltrating various tumors and organs across multiple species including primates, rodents, cetartiodactylans, and carnivores. We found that MDMs, including TAMs, do not express CD163 in mice. Our findings also suggest that murine CD163-positive macrophages likely originate from a specific subset of resident macrophages, namely fetal liver monocytes/macrophages, as indicated by fetal analysis. Furthermore, we revealed that the CD163-negative expression pattern in MDMs is a trait shared by the rodent clade.
Rodent MDMs do not express CD163, a phenotype not shared with MDMs of other mammals. Our findings caution against the extrapolation of rodent experimental results to other animal models.
CD163是一种清道夫受体，主要在各种哺乳动物物种的巨噬细胞表面表达，是抗炎（M2样）巨噬细胞的标志物。CD163阳性肿瘤相关巨噬细胞（TAM）的高密度与各种患者肿瘤的预后较差有关。有趣的是，对小鼠的研究表明，CD163阳性TAM仅浸润肿瘤组织的边缘，而非中心。基于这些观察结果，我们推测作为大多数TAM来源的循环单核细胞衍生巨噬细胞（MDM）在小鼠中不表达CD163。
我们检测了体外从健康动物分化而来的MDM以及浸润包括灵长类动物、啮齿动物、偶蹄目动物和食肉动物在内的多种物种的各种肿瘤和器官的正常、致病和致瘤巨噬细胞中CD163的表达。我们发现，包括TAM在内的MDM在小鼠中不表达CD163。我们的研究结果还表明，小鼠CD163阳性巨噬细胞可能起源于常驻巨噬细胞的一个特定亚群，即胎肝单核细胞/巨噬细胞，胎儿分析表明了这一点。此外，我们揭示了MDM中CD163阴性表达模式是啮齿动物进化枝共有的特征。
啮齿动物MDM不表达CD163，这是其他哺乳动物MDM不具备的表型。我们的研究结果提醒人们不要将啮齿动物的实验结果外推至其他动物模型。
