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continuous Expression of Interferon Regulatory Factor 4 Sustains cD8^(+)T cell Immunity against Tumor

Research 2024年第3期2023卷 433-444页

作者： Anze Yu Jinfei Fu Zheng Yin Hui Yan xiang Xiao Dawei Zou Xiaolong Zhang Xiongbing Zu xian c.li Wenhao chen Immunobiology and Transplant Science center Department of SurgeryHouston Methodist Research Institute and Institute for Academic MedicineHouston Methodist HospitalHoustonTXUSA Department of Urology First Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdongChina Systems Medicine and Bioengineering Department Houston Methodist Neal Cancer CenterHoustonTXUSA Department of Radiology Houston Methodist HospitalWeill Cornell MedicineHoustonTXUSA Department of Urology Xiangya HospitalCentral South UniversityChangshaHunanChina Department of Surgery Weill Cornell MedicineCornell UniversityNew YorkNYUSA.

T-cell-based immunotherapy is gaining momentum in cancer treatment;however,our comprehension of the transcriptional regulation governing T cell antitumor activity remains *** objective of this study was to explore the function of interferon regulatory factor 4(IRF4)in antitumor cD8^(+)T cells using the TRAMP-c1 prostate cancer and B16F10 melanoma *** achieve this,we generated an Irf4^(GFP-DTR) mouse strain and discovered that cD8^(+)tumor-infiltrating lymphocytes(TILs)expressing high levels of *** exhibited a more differentiated PD-1high cell *** administering diphtheria toxin to tumor-bearing Irf4^(GFP-DTR) mice,we partially depleted ***^(+)TILs and observed an accelerated tumor *** specifically explore the function of IRF4 in antitumor cD8^(+)T cells,we conducted 3 adoptive cell therapy(AcT)***,depleting ***^(+)cD8^(+)TILs derived from AcT significantly accelerated tumor growth,emphasizing their crucial role in controlling tumor ***,deleting the Irf4 gene in antitumor cD8^(+)T cells used for AcT led to a reduction in the frequency and effector differentiation of cD8^(+)TILs,completely abolishing the antitumor effects of ***,we performed a temporal deletion of the Irf4 gene in antitumor cD8^(+)T cells during AcT,starting from 20 days after tumor implantation,which significantly compromised tumor ***,sustained expression of IRF4 is essential for maintaining cD8^(+)T cell immunity in the melanoma model,and these findings carry noteworthy implications for the advancement of more potent immunotherapies for solid tumors.

关键词： sustained immunity implantation

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Transcriptional and epigenetic regulation of immune tolerance:roles of the NF-κB family members

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cellular & Molecular Immunology 2019年第4期16卷 315-323页

作者： Lei Zhang xiang Xiao Preston R.Arnold xian c.li Immunobiology and Transplant Science center and Department of Surgery Houston Methodist HospitalHoustonTXUSA Department of Surgery Weill Cornell Medical CollegeCornell UniversityNew YorkNYUSA

Immune tolerance is a highly regulated state and involves diverse *** to the induction of tolerance is the targeted modulation of T-cell activities(both effector and regulatory),in which transcription factors play a significant *** nuclear factor kappa-B(NF-κB)family is a family of transcription factors that not only are critically involved in diverse T-cell responses but also are regulated by many mechanisms to maintain tolerance and T-cell ***-κB,as a transcription factor,has been extensively studied in recent decades,and the molecular mechanisms that regulate NF-κB activities have been well ***,recent studies have revealed exciting new roles for NF-κB;in addition to its transcriptional activity,NF-κB can also activate diverse epigenetic mechanisms that mediate extensive chromatin remodeling of target genes to regulate T-cell *** this review article,we highlight recent discoveries and emerging opportunities in targeting NF-κB family members as well as their associated chromatin modifiers in the induction of immune tolerance and in the clinical treatment of immune diseases.

关键词： Immune tolerance NF-κB chromatin modifiers

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Inhibitory Receptors of the Immune System:Functions and Therapeutic Implications

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cellular & Molecular Immunology 2009年第6期6卷 407-414页

作者： Jian Zhang xiang Xiao Wentao liu Gulcin Demirci xian c.li The Transplant Institute Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMA 02215USA Beth Israel Deaconess Medical center Harvard Medical School330 Brookline AvenueCLS-605BostonMA 02215USA

The immune system has a remarkable ability to respond to seemingly endless *** essence,a productive immune response takes place along a well defined but treacherous line,that is to effectively eradicate pathogens,and at the same time avoid causing damage to self *** type of response is fine-tuned,at least in part,by a complex array of pathways that either promote or inhibit the activation of innate and adaptive immune *** effort has been focused on pathways that can support immune *** this article,we review specifically pathways that can inhibit immune responses and maintain immune homeostasis,highlighting our recent understanding on the role of inhibitory receptors that selectively engage the self MHc class I molecules and the B7 superfamily members,we also discuss the inhibitory Fc receptors and inhibitory cytokines and how such pathways,either individually or collectively,regulate innate and adaptive immune ***,we summarize new emerging approaches on how such negative pathways can be therapeutically modulated in various disease settings.

关键词： immunity tolerance regulation inflammation negative pathways

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Role of cD8^(+) regulatory T cells in organ transplantation

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Burns & Trauma 2014年第1期2卷 18-23页

作者： Jiyan Su Qingfeng Xie Yang Xu xian c.li Zhenhua Dai center for Regenerative and Translational Medicine Guangdong Provincial Academy of Chinese Medical SciencesGuangdong Provincial Hospital of Chinese Medicine and Guangzhou University of Chinese Medicine School of Chinese Material MedicaGuangzhouGuangdongChina Immunobiology and Transplantation Research center Houston Methodist Research InstituteHoustonTexasUSA

cD8^(+)T cells are regulatory T cells(Tregs)that suppress both alloimmunity and autoimmunity in many animal *** class of regulatory cells includes the cD8^(+)cD28^(-),cD8^(+)cD103^(+),cD8^(+)FoxP3^(+)and cD8^(+)cD122^(+)*** mechanisms of action of these regulatory cells are not fully understood;however,the secretion of immunosuppressive cytokines,such as interleukin(IL)-4,IL-10 and transforming growth factor beta(TGF-β)as well as the direct killing of target cells via Fas L/Fas and the perforin/granzyme B pathways have been demonstrated in various *** studies are necessary to fully understand the mechanisms underlying the suppressive effects of Tregs and to provide experimental support for potential clinical *** recently observed that cD8^(+)cD122^(+)Tregs more potently suppressed allograft rejection compared to their cD4^(+)cD25^(+)counterparts,supporting the hypothesis that cD8^(+)Tregs may represent a new and promising Treg family that can be targeted to prevent allograft rejection in the *** this review,we summarize the progress in the field during the past 7-10 years and discuss cD8^(+)Treg phenotypes,mechanisms of action,and their potential clinical applications;particularly in composite tissue transplants in burn and trauma patients.

关键词： Tolerance transplantation cD8^(+)regulatory T cell immune regulation

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天然免疫细胞的获得性免疫属性及其在移植排斥中的作用

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中华消化外科杂志 2022年第8期21卷 1044-1049页

作者：王光川 xian c.li 免疫生物学和移植科学中心休斯顿卫理公会医院德克萨斯医学中心休斯顿77030

移植排斥反应涉及天然免疫细胞和获得性免疫细胞。几十年来,获得性免疫细胞一直是移植免疫研究主要方向。研究者发现天然免疫细胞具有令人惊讶的新特征,包括免疫记忆,这可能对进一步改善移植物存活具有重要意义。移植物在短期内的存活... 详细信息

移植排斥反应涉及天然免疫细胞和获得性免疫细胞。几十年来,获得性免疫细胞一直是移植免疫研究主要方向。研究者发现天然免疫细胞具有令人惊讶的新特征,包括免疫记忆,这可能对进一步改善移植物存活具有重要意义。移植物在短期内的存活率非常好,但长期存活仍然较差,并且在临床上大多数移植物因慢性排斥而导致功能丢失(简称失功)。在动物模型和临床研究中,慢性排斥反应导致的移植物失功通常由天然免疫细胞主导,尤其是移植物中的巨噬细胞和自然杀伤细胞。最近的研究结果显示:天然免疫细胞可以表现出获得性免疫属性,其通过直接识别非己抗原,或在同种异体环境中被“训练”,从而表现出免疫记忆特征。在部分模型中,靶向这种天然免疫细胞获得性特征的治疗方法可以促进同种异体移植物长期存活。这些发现可能为促进临床移植物存活和恶性肿瘤以及自身免疫性疾病的治疗开辟新的治疗机会。笔者综合文献报道,介绍天然免疫细胞的获得性应答特征,通过充分讨论天然免疫细胞类型的异质性和可塑性,以及相关问题,激发研究者在该领域开展更多探索。

关键词：移植排斥反应天然免疫细胞免疫记忆自然杀伤细胞巨噬细胞

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The transcription factor RelB restrains group 2 innate lymphoid cells and type 2 immune pathology in vivo

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cellular & Molecular Immunology 2021年第1期18卷 230-242页

作者： Lei Zhang Yuanlin Ying Shuqiu chen Preston R.Arnold Fafa Tian Laurie J.Minze xiang Xiao xian c.li Immunobiology and Transplant Science center and Department of SurgeryHouston Methodist HospitalTexas Medical CenterHoustonTexasUSA Department of Neurology Xiangya HospitalCentral South UniversityChangshaChina Department of Urology Southeast University Zhongda HospitalNanjingChina Department of Surgery Weill Cornell Medical College of Cornell UniversityNew YorkNYUSA

The exact relationships between group 2 innate lymphoid cells(ILc2s)and Th2 cells in type 2 pathology,as well as the mechanisms that restrain the responses of these cells,remain poorly *** we examined the roles of ILc2s and Th2 cells in type 2 lung pathology in vivo using germline and conditional fie/b-deficient *** found that mice with germline deletion of Relb^(-/-)spontaneously developed prominent type 2 pathology in the lung,which contrasted sharply with mice with T-cell-specific Relb deletion(Relb^(f/f)cd4-cre),which were healthy with no observed autoimmune *** also found that in contrast to wild-type B6 mice,Rel6-defident mice showed markedly expanded ILc2s but not ILc1s or ***,adoptive transfer of naive cD4^(+)T cells into Rag1^(-/-)Relb^(-/-)hosts induced prominent type 2 lung pathology,which was inhibited by depletion of ***,we showed that Relb deletion led to enhanced expression of Bcl11b,a key transcription factor for *** concluded that RelB plays a critical role in restraining ILc2s,primarily by suppressing Bcl11b activity,and consequently inhibits type 2 lung pathology in vivo.

关键词： Allergic inflammation Innate lymphoid cells NF-kB RelB Th2 cells type 2 pathology

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New progress in immunobiology and transplantation research

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Burns & Trauma 2014年第1期2卷 1-2页

作者： xian c.li Department of Surgery Transplant Immunology ProgramHouston Methodist HospitalTexas Medical CenterHoustonTexas 77030USA

In this special issue of Burns&Trauma,we focus on transplant immunology,highlighting the pressing issues in the field and emerging strategies in resolving these issues,especially in the area of tolerance *** ultimate ... 详细信息

关键词： tolerance ultimate strategies

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The RNA helicase DHX15 is a critical regulator of natural killer-cell homeostasis and functions

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cellular & Molecular Immunology 2022年第6期19卷 687-701页

作者： Guangchuan Wang xiang Xiao Yixuan Wang Xiufeng chu Yaling Dou Laurie J.Minze Rafik M.Ghobrial Zhiqiang Zhang xian c.li Immunobiology and Transplant Science center and Department of Surgery Houston Methodist HospitalTexas Medical CenterHoustonTXUSA Department of Surgery Weill Cornell Medical College of Cornell UniversityNew YorkNYUSA

The RNA helicase DHX15 is widely expressed in immune cells and traditionally thought to be an RNA splicing factor or a viral RNA ***,the role of DHX15 in NK-cell activities has not been studied thus ***,we generated Dhx15-floxed mice and found that conditional deletion of Dhx15 in NK cells(Ncr1creDhx15fl/fl mice)resulted in a marked reduction in NK cells in the periphery and that the remaining Dhx15-deleted NK cells failed to acquire a mature *** a result,Dhx15-deleted NK cells exhibited profound defects in their cytolytic *** also found that deletion of Dhx15 in NK cells abrogated their responsiveness to IL-15,which was associated with inhibition of IL-2/IL-15Rβ(cD122)expression and IL-15R *** defects in Dhx15-deleted NK cells were rescued by ectopic expression of a constitutively active form of ***,DHX15 did not affect cD122 mRNA splicing and stability in NK cells but instead fac.litated the surface expression of cD122,likely through interaction with its 3′UTR,which was dependent on the ATPase domain of DHX15 rather than its splicing ***,our data identify a key role for DHX15 in regulating NK-cell activities and provide novel mechanistic insights into how DHX15 regulates the IL-15 signaling pathway in NK cells.

关键词： DEAH-box helicase 15(DHX15) Innate immunity Natural killer(NK)cells Homeostasis IL-15 signaling pathway

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Theoretical Design of Defects as a Driving Force for Ion Transport in li_(3)OBr Solid Electrolyte

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Energy & Environmental Materials 2024年第3期7卷 143-153页

作者： Xingyun Luo Yanlu li xian Zhao State Key Lab of crystal Materials and Institute of crystal Materials Shandong UniversityJinan 250100China center for Optics Research and Engineering Shandong UniversityQingdao 266237China

Due to ever-increasing concerns about safety issues in using li ionic batteries,solid electrolytes have extensively *** li-rich antiperovskite li_(3)OBr has been considered as a promising solid electrolyte candidate,but it still suffers challenges to achieve a high ionic conductivity owing to the high intrinsic symmetry of the crystal ***,we presented a design strategy that introduces various point defects and grain boundaries to break the high lattice symmetry of li_(3)OBr crystal,and their effect and microscopic mechanism of promoting the migration of li-ion were explored *** has been found that li_(i)are the dominant defects responsible for the fast li-ion diffusion in bulk li_(3)OBr and its surface,but they are easily trapped by the grain boundaries,leading to the annihilating of the Frenkel defect pair V'_(li)+li_(i),and thus limits the V'_(li)diffusion at the grain *** V_(Br)defect near the grain boundaries can effectively drive V'_(li)across the grain boundary,thereby converting the carrier of li^(+)migration from li,in the bulk and surface to V'_(li)at the grain boundary,and thus improving the ionic conductivity in the whole li_(3)OBr *** work provides a comprehensive insight into the li^(+)transport and conduction mechanism in the li_(3)OBr *** opens a new way of improving the conductivity for all-solid-state li electrolyte material through the defect design.

关键词： defects density functional theory ionic migration solid electrolyte

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Evaluation of transmission risk of respiratory particles under different ventilation strategies in an elevator

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Building Simulation 2024年第5期17卷 771-784页

作者： liangyu Zhu xian li Bujin Feng Fan liu School of civil Engineering and Architecture Linyi UniversityLinyi276000China college of Agriculture Shandong Agricultural UniversityTaian271018China School of Environment and Architecture University of Shanghai for Science and TechnologyShanghai200093China

People in elevators are at risk of respiratory infection because the elevator cabin is crowded and has poor *** exhaled particles may be inhaled by the susceptible person,deposited on the surface and suspended in the elevator,which can result in direct and indirect ***,whether the air vent designs adopted in the elevator can effectively reduce the transmission risk of respiratory particles remains *** this study,the dispersion of particles under four common ventilation strategies used in the commercial elevator was investigated by proven computational fluid dynamics(cFD)*** flow field was simulated with the RNG κ-ξ turbulence model and the Lagrangian method was adopted to track particle *** effects of air vent layout and airflow rate on particle transmission were *** found that more than 50% of exhaled particles(average value)were suspended in the cabin and difficult to discharge under the investigated ventilation *** deposited fraction of particles on the susceptible person reached up to 39.14% for infiltration ventilation,which led to a high risk of contact *** the ventilation rate could not significantly reduce the inhalation proportion of particles due to the poor airflow distribution inside the elevator.A more proper ventilation strategy should be explored for the elevator to control transmission risk.

关键词： particle dispersion transmission risk elevator ventilation strategy computational fluid dynamics(cFD)

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