1 Chun-Kwok WONG 黄振国 Biography Professor Chun-Kwok Wong is Professor of Department of Chemical Pathology, Faculty of Medicine, The Chinese University of Hong Kong (CUHK). He obtained his PhD degree in Immunology from the Department of Biochemistry, CUHK in 1993. This was followed by postdoctoral appointments at the Centre for Biochemical and Biophysical Science and Medicine of the Brigham and Women's Hospital, Harvard Medical School (1994- 1996), and the Pulmonary and Critical Care Unit at the Massachusetts General Hospital, Harvard Medical School, USA (1996-1997). He was appointed postdoctoral research fellow in the Department of Chemical Pathology, CUHK from August 1997 to June 2000, Scientific Officer in July 2000, Associate Professor in February 2001, and Professor in August 2009. He served as Director of Institute of Chinese Medicine, CUHK (2013- 2025). Professor Wong is also Honorary Scientific Officer (Medical) in the diagnostic clinical chemistry laboratory at Prince of Wales Hospital. Professor Wong was the former President of Hong Kong Society for Immunology and Hong Kong Society of Flow Cytometry, current Treasurer of the Hong Kong Society for Immunology and Hong Kong Society of Flow Cytometry, Fellow of Royal Society of Biology (FRSB), UK, and editorial board member of Cellular & Molecular Immunology, Journal of Leukocyte Biology etc. Research Interests: Immunology research includes (1) the elucidation of cytokine and chemokine network and intracellular signal transductions of immune effector cells including eosinophils, lymphocytes, mast cells, basophils and dendritic cells in inflammatory diseases, with recent emphasizing in the translational application of immunoregulatory cytokines, (2) the immunopathological mechanisms of allergic diseases, autoimmune diseases and infectious diseases and (3) the immunomodulatory, anti-infectious, anti-cancer and anti-allergic activities and underlying mechanisms of traditional Chinese medicine and natural products. He has published over 322 refereed papers in international journals (Web of Science Core Collection, H-index = 64).

2 黄振国教授现任香港中文大学医学院化学病理学系教授。他于 1993 年获香港中 文大学生物化学系免疫学博士学位。其后，他先后在美国哈佛医学院布莱根妇女 医院生物化学与生物物理科学及医学中心(1994-1996)以及麻省总医院肺科与重 症监护科(1996-1997)担任博士后研究员。1997 年 8 月至 2000 年 6 月，他获聘为 香港中文大学化学病理学系博士后研究员，2000 年 7 月晋升为科学主任，2001 年 2 月获聘为副教授，2009 年 8 月升任教授, 曾出任香港中文大学中医中药研 究所所长（2013-2025）。黄教授同时担任威尔斯亲王医院诊断临床化学实验室荣 誉科学主任(医学)。黄教授曾任香港免疫学会及香港流式细胞术学会主席，现任 香港免疫学会及香港流式细胞术学会司库，并为英国皇家生物学会院士(FRSB)和 Cellular & Molecular Immunology, Journal of Leukocyte Biology 等期刊的编辑委员会 成员。 研究方向： 免疫学研究涵盖以下领域：(1)阐明炎症性疾病中嗜酸性粒细胞、淋巴细胞、肥大 细胞、嗜碱性粒细胞及树突状细胞等免疫效应细胞的细胞因子与趋化因子网络及 细胞内信号转导机制，近期重点关注免疫调节性细胞因子的转化应用； (2) 过敏 性疾病、自身免疫性疾病及感染性疾病的免疫病理机制；(3) 中药与天然产物在 免疫调节、抗感染、抗癌及抗过敏方面的活性以及其内在机制。已在国际期刊发 表同行评审论文逾 322 篇(Web of Science 核心合集, H 指数=64)。

3 Immunological Mechanisms of Interleukin-40 in Modulating Macrophage and B cell Function for Promoting Inflammation in Allergic Asthma Abstract We investigated the role of interleukin-40 (IL-40), a novel B cell-associated cytokine, in lung inflammation associated with allergic asthma. Our findings revealed that IL-40 expression was significantly upregulated in both patients with allergic asthma and in a house dust mite (HDM)-induced murine model. Elevated IL-40 levels exacerbated airway hyperresponsiveness (AHR), promoted inflammatory cell infiltration, and increased the production of type 2 cytokines, indicating a key role in amplifying allergic airway inflammation. Importantly, treatment with a neutralizing antibody against IL-40 significantly alleviated airway inflammation, suggesting its therapeutic potential. Mechanistically, the pro-inflammatory effects of IL-40 were closely associated with alterations in macrophage polarization and B cell development. Macrophages exhibited the highest induction of IL-40 secretion following allergen exposure and responded most strongly to IL-40 stimulation. This response involved activation of the JAK/STAT1 and p38-MAPK signaling pathways, driving their polarization toward a pro-inflammatory phenotype while inhibiting the differentiation of a specific Arg1+ macrophage subset. Moreover, T cells did not display a direct response to IL-40 stimulation. In addition, IL-40 was essential for normal B cell development. IL-40-/- mice showed a marked reduction in pre-B cells in the bone marrow and impaired B cell maturation in the spleen, characterized by decreased follicular B cell populations. Genes involved in B cell receptor synthesis and complement activation were notably downregulated in IL-40-/- mice. Collectively, these findings identify IL-40 as a pivotal regulator of allergic asthma, integrating innate and adaptive immune responses, and offering a novel avenue for therapeutic intervention.

4 白细胞介素-40 通过调节巨噬细胞和 B 细胞功能促进过敏性哮喘炎症的免疫机制 摘要 我们研究了新型 B 细胞相关细胞因子白细胞介素-40(IL-40)在过敏性哮喘相关肺 部炎症中的作用。研究发现，过敏性哮喘患者及尘螨诱导的小鼠模型中 IL-40 表 达均显着上调。升高的 IL-40 水平加剧气道高反应性(AHR)、促进炎性细胞浸润 并增加Ⅱ型细胞因子分泌，表明其在放大过敏性气道炎症中起关键作用。值得注 意的是，使用针对 IL-40 的中和抗体治疗显着缓解了气道炎症，表明其具有治疗 潜力。从机制上讲，IL-40 的促炎作用与巨噬细胞极化及 B 细胞发育的改变密切 相关。巨噬细胞在过敏原暴露后呈现最高水平的 IL-40 分泌诱导，并对 IL-40 刺 激作出最强反应。该反应涉及 JAK/STAT1 和 p38-MAPK 信号通路的激活，推动 巨噬细胞向促炎表型极化，同时抑制特定 Arg1+巨噬细胞亚群的分化。此外，T 细胞对 IL-40 刺激未表现出直接反应。同时，IL-40 对 B 细胞的正常发育至关重 要。IL-40-/-小鼠骨髓中前 B 细胞数量显着减少，脾脏内 B 细胞成熟受阻，表现 为滤泡 B 细胞群数量下降。参与 B 细胞受体合成和补体活化的基因在 IL-40-/-小 鼠中明显下调。 综合而言，这些发现揭示 IL-40 作为过敏性哮喘的关键调控因 子，整合了先天与适应性免疫反应，为治疗干预提供了全新途径。