来源：科技日报 为解析肝脏中巨噬细胞的空间排布和分子表型，研究人员运用前期发展的Liver-CUBIC光透明成像技术 与显微光学断层成像技术，对CX3CR1-GFP小鼠的完整肝叶开展单细胞分辨率成像。研究人员发现，在 肝脏汇管区，肝脏中的CX3CR1阳性细胞密集分布且具备独特转录特征。研究人员结合单细胞转录组测 序分析，将该细胞群命名为肝脏汇管区巨噬细胞亚群。 研究发现，肝脏汇管区巨噬细胞亚群不仅在肝脏免疫稳态中扮演关键角色，还在神经保护方面发挥重要 作用。肝脏汇管区巨噬细胞亚群能够捕获肝实质细胞来源的抗原，与汇管区T细胞形成稳定接触以参与 免疫反应调节，还能够通过与肝脏交感神经直接接触来保护神经结构。 在非酒精性脂肪肝炎小鼠模型中发现，肝脏汇管区巨噬细胞亚群缺失会使中性粒细胞浸润增加，并加剧 交感神经损伤。这些发现进一步证实其在维持肝脏免疫稳态和神经保护中的重要性。 这一研究揭示了肝脏汇管区巨噬细胞亚群在免疫稳态和神经保护中的作用，深化了对肝脏汇管区巨噬细 胞亚群空间异质性的认知，为肝脏免疫学和神经免疫学提供新见解，也为相关疾病治疗提供潜在新靶 标。《自然免疫》在同期配发的新闻与观点文章中指出，该研究将有助 ...

Core Viewpoint - The research identifies a unique subset of liver portal macrophages (LPAM) that play a crucial role in maintaining liver immune homeostasis and have neuroprotective functions [3][6]. Group 1: Research Findings - The study published in Nature Immunology reveals the existence of a distinct LPAM network characterized by CX3CR1+ CD63+ cells, which differ significantly in transcription and spatial distribution from CX3CR1+ CD207+ liver capsule macrophages [5]. - LPAM survival is dependent on the colony-stimulating factor-1 receptor (CSF1R), and these cells are established in the liver portal area post-birth, supplemented by bone marrow-derived cells during liver homeostasis [5]. - During non-alcoholic steatohepatitis (NASH), the absence of LPAM leads to increased neutrophil infiltration and exacerbates sympathetic nerve degeneration [5]. Group 2: Implications for Liver Health - The findings suggest that the liver portal area is a critical region for regulating liver homeostasis and disease, with tissue macrophages capturing antigens, protecting sympathetic nerves, and limiting neutrophil recruitment during inflammation [7].

Core Insights - The research conducted by the Shanghai Institute of Nutrition and Health reveals the molecular mechanism of APOL9 protein's specific binding to gut microbiota, which plays a crucial role in maintaining intestinal immune homeostasis [1][2] - APOL9 protein acts as a "bacterial diplomat," inducing specific bacteria to release outer membrane vesicles (OMVs) that enhance the host's immune response [1][2] Group 1: Research Findings - The study published in the journal "Nature" highlights that APOL9 does not kill target bacteria but instead promotes the release of OMVs, which are rich in bacterial molecules that can be captured by the host immune system [1] - OMVs activate the interferon-γ signaling pathway and increase the expression of MHC-II molecules on intestinal cells, leading to the training of a specific type of T cells that maintain intestinal immune stability [1][2] Group 2: Experimental Validation - To validate the physiological function of APOL9, the research team created APOL9 gene knockout mice, which showed uncontrolled bacterial spread and increased mortality when infected with Salmonella [2] - Supplementing these knockout mice with OMVs significantly improved infection symptoms and enhanced immune responses, demonstrating the active role of host proteins in shaping beneficial immune reactions [2]

Core Insights - AnaptysBio's investigational drug rosnilimab shows a best-in-disease profile for treating moderate-to-severe rheumatoid arthritis (RA), demonstrating JAK-like efficacy and durable responses [1][2][3] Efficacy and Clinical Outcomes - In a Phase 2b trial with 424 patients, rosnilimab achieved significant clinical improvements, including low disease activity (LDA) and remission on the Clinical Disease Activity Index (CDAI) [1][2][3] - By Week 12, 45% of patients achieved CDAI LDA, increasing to 69% by Week 14, indicating a strong response to treatment [3][4] - Rosnilimab demonstrated a rapid onset of ACR20 response, comparable to upadacitinib, with a substantial decrease in C-reactive protein (CRP) levels [2][3] Safety and Tolerability - Rosnilimab exhibited a favorable safety profile, with no treatment-related serious adverse events (SAEs) reported and a low incidence of injection site reactions [10][11] - Less than 2% of patients discontinued treatment due to adverse events, indicating good tolerability [10][11] Market Potential - The findings suggest rosnilimab could capture a significant share of the ~$20 billion U.S. RA market, with potential for extended dosing intervals [2][3] - The company aims to complete ongoing studies for rosnilimab in ulcerative colitis, with initial data expected in Q4 2025 [2][14] Mechanism of Action - Rosnilimab targets PD-1+ T cells, aiming to restore immune homeostasis and reduce inflammation associated with RA [19][21] - The drug demonstrated a ~90% reduction in PD-1 T cells and a ~50% reduction in PD-1+ T cells, indicating robust pharmacological activity [8][19] Future Developments - AnaptysBio plans to advance rosnilimab's clinical development and explore its application in other autoimmune diseases [21][22] - The company is committed to developing innovative treatments that address the long-term needs of patients with chronic inflammatory conditions [21][22]

撰文丨王聪 编辑丨王多鱼 排版丨水成文 哺乳动物 （包括人类） 的肠道内寄居着数以万亿计的共生菌，它们通过各种生物活性分子与宿主相互作 用。然而，宿主为从这些共生关系中获益而进化出的互利策略，在很大程度上尚未得到探索。 2025年5月14日，中国科学院上海营养与健康研究所 钱友存 团队联合 中国科学院分子细胞科学卓越创新 中心 宋昕阳 团队 （ 杨涛 、 胡孝虎 、 曹飞 为论文共同第一作者 ） ，在国际顶尖学术期刊 Nature 上 发 表了题为： Targeting symbionts by apolipoprotein L proteins modulates gut immunity 的研究论文。 该研究首次揭示了小鼠 肠道上皮细胞 （IEC） 分泌的载脂蛋白 APOL9a/b 及其人源同源蛋白 APOL2 可 特异性识别 拟杆菌目 （Bacteroidales） 细菌，诱导其释放 外膜囊泡 （OMV） ，进而激活宿主免疫因子 IFN-γ-MHC-II 信号通路，提升肠道黏膜屏障的抗感染能力。 这项研究不仅扩展了我们对宿主-共生菌在共同进化过程中互作机制的理解，也为开发新型微生态干预策略 提供了理论支 ...

行 业 研 究 华福证券 医药生物 2025 年 05 月 11 日 脓毒症：免疫稳态疗法迎来新突破，建议关注远 大医药 投资要点： 行 业 定 期 报 告 行情回顾：本周（2025 年 5 月 6 日- 2025 年 5 月 9 日）中信医药指数 上涨 1.0%，跑输沪深 300 指数 1.0 pct，在中信一级行业分类中排名第 26 位；2025 年初至今中信医药生物板块指数上涨 1.3%，跑赢沪深 300 指数 3.6pct，在中信行业分类中排名第 13 位。本周涨幅前五的个股为：常山药 业（+23.59%）、海创药业（+22.76%）、香雪制药（+19.64%）、金凯生 科（+18.98%）、南华生物（+16.46%）。 脓毒症——免疫稳态疗法迎来新突破，建议关注远大医药：脓毒症 （Sepsis）是感染、严重创（烧、战）伤、外科大手术、休克等重症患者的 一种常见并发症，进一步发展可导致多器官功能障碍综合征 (MODS)，是 临床危重患者的最主要死亡原因之一。脓毒症可以由任何部位的感染引起。 （1）脓毒症患者众多，死亡率高。根据文献数据，2017 年全球约有 4890 万脓毒症患者，年死亡人数达 110 ...