Memida Takumi, Cao Guoqin, Dalir Abdolahinia Elaheh, Ruiz Sunniva, Huang Shengyuan, Hassantash Sahar, Shindo Satoru, Okamoto Motoki, Yamashita Shohei, Nakamura Shin, Suzuki Maiko, Kawai Toshihisa, Han Xiaozhe
Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University, 3301 South University Drive, Fort Lauderdale, FL 33314, USA.
Cells. 2025 Jun 7;14(12):860. doi: 10.3390/cells14120860.
Regulatory B cells (B regs) are immune cells that help suppress excessive inflammatory responses by interacting with other immune components. Among them, B-10 cells are known for their strong immunoregulatory function. This study focused on how B-10 cells influence macrophage phenotype and function through the PD-1 signaling pathway. To investigate this, B-10 cells derived from mouse spleens were co-cultured with bone marrow-derived macrophages (BMDMs) from either wild-type (WT) or PD-1 knockout (PD-1 KO) mice, using both direct contact and Transwell setups. The findings indicated that direct co-culture with B-10 cells significantly promoted the polarization of macrophages towards the anti-inflammatory M2 type, characterized by increased expression of surface markers (F4/80, CD206, CD163), higher levels of PD-1, and upregulation of M2-related genes (, , , , and ). These macrophages also exhibited enhanced phagocytic activity and greater secretion of specialized pro-resolving mediator (SPMs) like RvD2 and 15-epi LXA4. In contrast, these effects were reduced when B-10 cells were cultured indirectly or when PD-1 was absent. These findings suggest that B-10 cells promote anti-inflammatory macrophage activity primarily through PD-1 signaling, offering insights into potential therapeutic approaches for controlling inflammation.
调节性B细胞(Bregs)是一类免疫细胞,通过与其他免疫成分相互作用来帮助抑制过度的炎症反应。其中,B-10细胞以其强大的免疫调节功能而闻名。本研究聚焦于B-10细胞如何通过PD-1信号通路影响巨噬细胞的表型和功能。为了探究这一点,将从小鼠脾脏中分离得到的B-10细胞与来自野生型(WT)或PD-1基因敲除(PD-1 KO)小鼠的骨髓来源巨噬细胞(BMDMs)进行共培养,采用直接接触和Transwell培养两种方式。研究结果表明,与B-10细胞直接共培养显著促进巨噬细胞向抗炎性M2型极化,其特征为表面标志物(F4/80、CD206、CD163)表达增加、PD-1水平升高以及M2相关基因(、、、和)上调。这些巨噬细胞还表现出增强的吞噬活性以及RvD2和15-表异构LXA4等特异性促消退介质(SPMs)分泌增加。相比之下,当B-10细胞间接培养或不存在PD-1时,这些效应会减弱。这些发现表明,B-10细胞主要通过PD-1信号通路促进抗炎性巨噬细胞活性,为控制炎症的潜在治疗方法提供了见解。