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Eosinophils promote CD8+ T cell memory generation to potentiate anti-bacterial immunity

Signal Transduction and Targeted Therapy 2024年第3期9卷 1230-1243页

作者： Jun Zhou Jiaqi Liu Bingjing Wang Nan Li Juan Liu Yanmei Han xuetao cao Institute of Immunology Zhejiang University School of MedicineHangzhou 310058China National Key Laboratory of Immunity and Inflammation Institute of ImmunologyNaval Medical UniversityShanghai 200433China Department of Immunology Center for ImmunotherapyInstitute of Basic Medical SciencesPeking Union Medical CollegeChinese Academy of Medical SciencesBeijing 100005China Institute of Immunology College of Life SciencesNankai UniversityTianjin 300071China

Memory CD8+T cell generation is crucial for pathogen elimination and effective vaccination against *** cellular and molecular circuitry that underlies the generation of memory CD8+T cells remains *** can modulate inflammatory allergic responses and interact with lymphocytes to regulate their functions in immune *** we report that eosinophils are required for the generation of memory CD8+T cells by inhibiting CD8+T cell ***-deficient mice display significantly impaired memory CD8+T cell response and weakened resistance against Listeria monocytogenes(L.m.)***,eosinophils secrete interleukin-4(IL-4)to inhibit JNK/Caspase-3 dependent apoptosis of CD8+T cells upon *** in ***,active eosinophils are recruited into the spleen and secrete more IL-4 to suppress CD8+T cell apoptosis during early stage of *** in *** transfer of wild-type(WT)eosinophils but not IL-4-deficient eosinophils into eosinophil-deficient mice could rescue the impaired CD8+T cell memory ***,our findings suggest that eosinophil-derived IL-4 promotes the generation of CD8+T cell memory and enhances immune defense against *** study reveals a new adjuvant role of eosinophils in memory T cell generation and provides clues for enhancing the vaccine potency via targeting eosinophils and related cytokines.

关键词： impaired immunity spleen

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The RNA m^(6)A demethylase ALKBH5 drives emergency granulopoiesis and neutrophil mobilization by upregulating G-CSFR expression

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Cellular & Molecular Immunology 2024年第1期21卷 6-18页

作者： Yang Liu Renjie Song Zhike Lu Lu Zhao Xinyi Zhan Yini Li xuetao cao Department of Immunology Center for ImmunotherapyInstitute of Basic Medical SciencesPeking Union Medical CollegeChinese Academy of Medical SciencesBeijingChina Suzhou Institute of Systems Medicine Chinese Academy of Medical SciencesSuzhouChina Frontier Research Center for Cell Response Institute of ImmunologyCollege of Life SciencesNankai UniversityTianjinChina School of Life Sciences Westlake UniversityHangzhouChina

Emergency granulopoiesis and neutrophil mobilization that can be triggered by granulocyte colony-stimulating factor(G-CSF)through its receptor G-CSFR are essential for antibacterial innate ***,the epigenetic modifiers crucial for intrinsically regulating G-CSFR expression and the antibacterial response of neutrophils remain largely unclear.N6-methyladenosine(m^(6)A)RNA modification and the related demethylase alkB homolog 5(ALKBH5)are key epigenetic regulators of immunity and inflammation,but their roles in neutrophil production and mobilization are still *** used cecal ligation and puncture(CLP)-induced polymicrobial sepsis to model systemic bacterial infection,and we report that ALKBH5 is required for emergency granulopoiesis and neutrophil ***5 depletion significantly impaired the production of immature neutrophils in the bone marrow of septic *** addition,Alkbh5-deficient septic mice exhibited higher retention of mature neutrophils in the bone marrow and defective neutrophil release into the circulation,which led to fewer neutrophils at the infection site than in their wild-type *** bacterial infection,ALKBH5 imprinted production-and mobilization-promoting transcriptome signatures in both mouse and human ***,ALKBH5 erased m^(6)A methylation on the CSF3R mRNA to increase the mRNA stability and protein expression of G-CSFR,consequently upregulating cell surface G-CSFR expression and downstream STAT3 signaling in *** RIP-qPCR results confirmed the direct binding of ALKBH5 to the CSF3R mRNA,and the binding strength declined upon bacterial infection,accounting for the decrease in G-CSFR expression on bacteria-infected *** these results collectively,we define a new role of ALKBH5 in intrinsically driving neutrophil production and mobilization through m^(6)A demethylation-dependent posttranscriptional regulation,indicating that m^(6)A RNA modification in neutrop

关键词： Emergency granulopoiesis Neutrophil mobilization ALKBH5 m^(6)A RNA modification G-CSF receptor

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Nutritional competition within tumor microenvironment dictates anti-tumor immunity

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National Science Review 2024年第2期11卷 98-100页

作者： Yankang Fei xuetao cao Juan Liu National Key Laboratory of Immunity and Inflammation Institute of Immunology Naval Medical University Department of Immunology Chinese Academy of Medical Sciences Institute of Immunology College of Life Sciences Nankai University

The crosstalk between metabolism and immunity has emerged as an essential regulator of tumor immune escape, and targeting immunometabolic pathways holds great potential for cancer immunotherapy [1]. Abnormal metabolic...

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聚焦生物医药前沿领域引领我国医学科学发展

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中华医学杂志 2024年第1期104卷 1-4页

作者：曹雪涛国家卫生健康委北京100044 中国医学科学院免疫治疗研究中心北京100005

随着生物医学领域基础研究和技术创新不断取得突破,人们对生命本质和发病机制有了更深认识,新型医疗技术与药品器械不断涌现,极大地推动了疾病的诊断、治疗、预防以及健康维护。如何瞄准国际前沿和行业自身发展需求,实现高质量发展,是... 详细信息

随着生物医学领域基础研究和技术创新不断取得突破,人们对生命本质和发病机制有了更深认识,新型医疗技术与药品器械不断涌现,极大地推动了疾病的诊断、治疗、预防以及健康维护。如何瞄准国际前沿和行业自身发展需求,实现高质量发展,是我国生物医学界的一项重大任务。本文强调进一步加强我国医学科学交叉融合发展、实现医学研究范式变革、推动革命性医疗技术与新型药品器械研制应用,并展望了生物医药领域需要关注的18个前沿热点和共性问题。

关键词：医药卫生前沿领域技术创新医疗发展

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2023年国内外免疫学研究重要进展

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中国免疫学杂志 2024年第1期40卷 1-10页

作者：刘娟曹雪涛海军军医大学免疫学研究所暨免疫与炎症全国重点实验室中国医学科学院免疫治疗研究中心

2023年，免疫学仍活跃在生命科学和医学创新的最前沿，取得了诸多免疫学根本核心问题上的理论进步以及具有重要临床应用和转化价值的技术突破。本文遴选了2023年国内外免疫学领域的代表性研究成果，与同行们共同回顾过往、展望未来。疏... 详细信息

2023年，免疫学仍活跃在生命科学和医学创新的最前沿，取得了诸多免疫学根本核心问题上的理论进步以及具有重要临床应用和转化价值的技术突破。本文遴选了2023年国内外免疫学领域的代表性研究成果，与同行们共同回顾过往、展望未来。疏漏之处敬请批评指正。

关键词：免疫应答免疫细胞免疫代谢细胞死亡神经免疫炎症肿瘤免疫

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Antibody variable region engineering for improving cancer immunotherapy

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Cancer Communications 2022年第9期42卷 804-827页

作者： Hantao Lou xuetao cao Ludwig Institute of Cancer Research University of OxfordOxford OX37DRUK Chinese Academy for Medical Sciences Oxford Institute Nuffield Department of MedicineUniversity of OxfordOxford OX37FZUK Department of Immunology Centre for ImmunotherapyInstitute of Basic Medical SciencesChinese Academy of Medical SciencesBeijing 100005P.R.China

The efficacy and specificity of conventional monoclonal antibody(mAb)drugs in the clinic require further ***,the development and application of novel antibody formats for improving cancer immunotherapy have attracted much *** region-retaining antibody fragments,such as antigen-binding fragment(Fab),single-chain variable fragment(scFv),bispecific antibody,and bi/trispecific cell engagers,are engineered with humanization,multivalent antibody construction,affinity optimization and antibody masking for targeting tumor cells and killer cells to improve antibody-based therapy potency,efficacy and *** this review,we summarize the application of antibody variable region engineering and discuss the future direction of antibody engineering for improving cancer therapies.

关键词： antibody engineering bi/trispecific killer engager cancer immunotherapy chimeric antigen receptor-T(CAR-T)cell nanobody natural killer(NK)cell scFv

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Reversing epigenetic repression of transposable elements for improving tumor immunogenicity

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Cancer Communications 2022年第3期42卷 266-268页

作者： Xi Wang Qian Zhang xuetao cao Institute of Immunology Zhejiang University School of MedicineHangzhouZhejiang 310058P.R.China National Key Laboratory of Medical Immunology Institute of ImmunologyNaval Medical UniversityShanghai 200433P.R.China

In a recent study published in Nature,Zhang et al.[1]revealed a new epigenetic mechanism for restraining tumor intrinsic immunogenicity:Lysine demethylase 5B(KDM5B)recruits SET domain bifurcated histone lysine methyltransferase 1(SETDB1)to repress the transcription of transposable elements(TEs)by H3K9me3 modifica-tion,while TE de-repression by targeting KDM5B conse-quently activated nucleic acid sensing pathways and anti-gen presentation to elicit tumor intrinsic immunity which enhanced host anti-tumor immune response.

关键词： elements restrain tumor

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Long noncoding RNAs in innate immunity

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Cellular & Molecular Immunology 2016年第2期13卷 138-147页

作者： Yuan Zhang xuetao cao National Key Laboratory of Medical Molecular Biology & Department of Immunology Institute of Basic Medical Sciences Chinese Academy of MedicalSciences Beijing 100005 China

Long noncoding RNAs （IncRNAs） have been shown to play important roles in immune cell development and immune responses through different mechanisms, such as dosage compensation, imprinting, enhancer function, and transcriptional regulation. Although the functions of most IncRNAs are unclear, some IncRNAs have been found to control transcriptional or post-transcriptional regulation of the innate and adaptive immune responses via new methods of protein-protein interactions or pairing with DNA and RNA. Interestingly, increasing evidence has elucidated the importance of IncRNAs in the interaction between hosts and pathogens. In this review, an overview of the IncRNAs modes of action, as well as the important and diversified roles of IncRNAs in immunity, are provided, and an emerging paradigm of IncRNAs in regulating innate immune responses is highlighted.

关键词： host-pathogen interaction innate immunity long noncoding RNA

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Interleukin-17 and its expanding biological functions

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Cellular & Molecular Immunology 2010年第3期7卷 164-174页

作者： Sheng Xu xuetao cao National Key Laboratory of Medical Immunology&Institute of Immunology Second Military Medical UniversityShanghaiChina

Interleukin-17(IL-17)and IL-17-producing cells have been shown to play important roles in inflammation and the immune ***-17 is believed to be mainly produced by T helper 17(Th17)cells,a unique helper T-cell subset different from Th1 and Th2 *** subsets of T cells such as cdT and natural killer T(NKT)cells have also been found to produce IL-17 in response to innate ***-17 acts as a proinflammatory cytokine that can induce the release of certain chemokines,cytokines,matrix metalloproteinases(MMPs)and antimicrobial peptides from mesenchymal and myeloid *** leads to the expansion and accumulation of neutrophils in the innate immune system and links innate and adaptive immunity in ***,increasing evidence indicates that IL-17 and IL-17-producing cells are involved in the pathogenesis of various diseases such as allergies,autoimmune diseases,allograft transplantation and even *** may also play protective roles in host defense against infectious diseases and promote induction of cytotoxic T lymphocyte(CTL)responses against *** of the IL-17 axis is under investigation for the treatment of inflammatory disorders.

关键词： autoimmune disease immunity interleukin-17 neutrophil T cells

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Cellular and molecular regulation of innate inflammatory responses

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Cellular & Molecular Immunology 2016年第6期13卷 711-721页

作者： Juan Liu xuetao cao National Key Laboratory of Medical Immunology & Institute of Immunology Second Military Medical University Shanghai 200433 China National Key Laboratory of Medical Molecular Biology Department of Immunology & Center for Immunotherapy Institute of Basic Medical Sciences Peking Union Medical College Chinese Academy of Medical Sciences Beijing 100005 China

Innate sensing of pathogens by pattern-recognition receptors （PRRs） plays essential roles in the innate discrimination between self and non-self components, leading to the generation of innate immune defense and inflammatory responses. The initiation, activation and resolution of innate inflammatory response are mediated by a complex network of interactions among the numerous cellular and molecular components of immune and non- immune system. While a controlled and beneficial innate inflammatory response is critical for the elimination of pathogens and maintenance of tissue homeostasis, dysregulated or sustained inflammation leads to pathological conditions such as chronic infection, inflammatory autoimmune diseases. In this review, we discuss some of the recent advances in our understanding of the cellular and molecular mechanisms for the establishment and reJzulation of innate immunity and inflammatory responses.

关键词： dendritic cells inflammation innate lymphoid cells innate signaling pattern-recognition receptors (PRRs)

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