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Intricacies of TGF-βsignaling in Treg and Th17 cell biology

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Cellular & Molecular Immunology 2023年第9期20卷 1002-1022页

作者： Junying wang Xingqi Zhao yisong y.wan Lineberger Comprehensive Cancer Center University of North Carolina at Chapel HillChapel HillNC 27599USA Department of Microbiology and Immunology University of North Carolina at Chapel HillChapel HillNC 27599USA

Balanced immunity is pivotal for health and ***4+helper T(Th)cells are central to the balance between immune tolerance and immune *** cells adopt distinct functions to maintain tolerance and clear *** of Th cell function often leads to maladies,including autoimmunity,inflammatory disease,cancer,and *** T(Treg)and Th17 cells are critical Th cell types involved in immune tolerance,homeostasis,pathogenicity,and pathogen *** is therefore critical to understand how Treg and Th17 cells are regulated in health and *** are instrumental in directing Treg and Th17 cell *** evolutionarily conserved TGF-β(transforming growth factor-β)cytokine superfamily is of particular interest because it is central to the biology of both Treg cells that are predominantly immunosuppressive and Th17 cells that can be proinflammatory,pathogenic,and immune *** TGF-βsuperfamily members and their intricate signaling pathways regulate Treg and Th17 cell function is a question that has been intensely investigated for two ***,we introduce the fundamental biology of TGF-βsuperfamily signaling,Treg cells,and Th17 cells and discuss in detail how the TGF-βsuperfamily contributes to Treg and Th17 cell biology through complex yet ordered and cooperative signaling networks.

关键词： TGF-beta regulatory T cell Th17 cell Treg

An essential role for TAK1 in the contact hypersensitivity response

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Cellular & Molecular Immunology 2011年第4期8卷 315-324页

作者： yan G Zhao yunqi wang Weidong Hao yisong y wan Department of Toxicology School of Public HealthPeking UniversityBeijingChina Department of Microbiology and Immunology Lineberger Comprehensive Cancer CenterUniversity of North Carolina at Chapel HillNCUSA

Contact hypersensitivity(CHS)is a delayed-type hypersensitivity that can be induced by haptens,such as 2,4-dinitrofluorobenzene(DNFB).Innate and adaptive immunities are both important for the development of *** treat CHS-related diseases,such as allergic contact dermatitis,a disease prevalent in industrialized countries,ways of interfering with improper immune function during CHS responses need to be *** growth factor-b-activated kinase-1(TAK1),a member of mitogen-activated protein kinase kinase kinase family,is important for both innate and adaptive *** thus hypothesized that the CHS response could be inhibited by interfering with TAK1 *** a mouse model in which TAK1 deletion can be locally induced,we observed that TAK deficiency led to an impaired CHS response and was associated with defective T-cell expansion,activation and interferon(IFN)-c *** addition,we investigated the effect of deleting TAK1 specifically in dendritic cells(DC)on the CHS *** found that when TAK1 is deficient in DC,the CHS response was abolished and hapten-elicited T-cell responses were ***,this study demonstrates an essential role of TAK1 in the induction of CHS and suggests that targeting TAK1 could be a viable approach to treat CHS.

关键词： CHS DC 2,4-dinitrofluorobenzene(DNFB) TAK1

The SKI proto-oncogene restrains the resident CD103^(+)CD8^(+) T cell response in viral clearance

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Cellular & Molecular Immunology 2021年第10期18卷 2410-2421页

作者： Bing Wu Ge Zhang Zengli Guo Gang wang Xiaojiang Xu Jian-liang Li Jason K.Whitmire Junnian Zheng yisong y.wan Lineberger Comprehensive Cancer Center School of MedicineUniversity of North Carolina at Chapel HillChapel HillNC 27599USA Department of Microbiology and Immunology School of MedicineUniversity of North Carolina at Chapel HillChapel HillNC 27599USA Department of Immunology College of Basic Medical ScienceDalian Medical UniversityDalianLiaoning 116044China Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy Cancer InstituteXuzhou Medical UniversityXuzhouJiangsu221002China Integrative Bioinformatics National Institute of Environmental Health SciencesResearch Triangle ParkChapel HillNC 27709USA Department of Genetics School of MedicineUniversity of North Carolina at Chapel HillChapel HillNC 27599USA

Acute viral infection causes illness and *** addition,an infection often results in increased susceptibility to a secondary infection,but the mechanisms behind this susceptibility are poorly *** its initial identification as a marker for resident memory CD8^(+)T cells in barrier tissues,the function and regulation of CD103 integrin(encoded by ITGAE gene)have been extensively ***,the function and regulation of the resident CD103^(+)CD8^(+)T cell response to acute viral infection remain *** TGFβsignaling is essential for CD103 expression,the precise molecular mechanism behind this regulation is ***,we reveal a TGFβ–SKI–Smad4 pathway that critically and specifically directs resident CD103^(+)CD8^(+)T cell generation for protective immunity against primary and secondary viral *** found that resident CD103^(+)CD8^(+)T cells are abundant in both lymphoid and nonlymphoid tissues from uninfected ***103 acts as a costimulation signal to produce an optimal antigenic CD8^(+)T cell response to acute viral *** is a reduction in resident CD103^(+)CD8^(+)T cells following primary infection that results in increased susceptibility of the host to secondary ***,CD103 expression inversely and specifically correlates with SKI proto-oncogene(SKI)expression but not R-Smad2/3 *** expression of SKI restricts CD103 expression in CD8^(+)T cells in vitro and in vivo to hamper viral ***,SKI is recruited to the Itgae loci to directly suppress CD103 transcription by regulating histone acetylation in a Smad4-dependent *** study therefore reveals that resident CD103^(+)CD8^(+)T cells dictate protective immunity during primary and secondary *** with SKI function may amplify the resident CD103^(+)CD8^(+)T cell response to promote protective immunity.

关键词： CD103 TGFβ SKI Smad4 LCMV infection Histone acetylation

Growth of RB Population in the Conversion Phase of Chlamydia Life Cycle

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Communications on Applied Mathematics and Computation 2024年第1期6卷 90-112页

作者： Frederic y.M.wan Department of Mathematics University of CaliforniaIrvineCA92697-3875USA

Upon infecting a host cell,the reticulate body(RB)form of the Chlamydia bacteria simply proliferates by binary fission for an extended *** data show only RB units in the infected cells 20 hours post infection(hpi),spanning nearly half way through the development *** data collected every 4 hpi,conversion to the elementary body(EB)form begins abruptly at a rapid rate sometime around 24 *** modeling proliferation and conversion as simple birth and death processes,it has been shown that the optimal strategy for maximizing the total(mean)EB population at host cell lysis time is a bang-bang control qualitatively replicating the observed conversion ***,the simple birth and death model for the RB proliferation and conversion to EB deviates in a significant way from the available data on the evolution of the RB population after the onset of RB-to-EB *** working with a more refined model that takes into account a small size threshold eligibility requirement for conversion noted in the available data,we succeed in removing the deficiency of the previous models on the evolution of the RB population without affecting the optimal bang-bang conversion strategy.

关键词： Chlamydia Life cycle Optimal control Maximal infectious spread Specie competitive survival

A method for analyzing on-line video images of crystallization at high-solid concentrations

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Particuology 2008年第1期6卷 9-15页

作者： Jian wan Cai y. Ma Xue Z. wang Institute of Particle Science and Engineering School of Process Environmental and Materials Engineering University of Leeds Leeds LS2 9JT UK

Recent research has demonstrated that on-line video imaging is a very promising technique for monitoring crystallization processes. The bottleneck in applying the technique for real-time closed-loop control is considered as image analysis that needs to be robust, fast and able to handle varied image qualities due to temporal variations of operating conditions such as mixing and solid concentrations. Image analysis at highsolid concentrations turns out to be extremely challenging because crystals tend to overlap or attach to each other and the boundaries between the crystals are usually ambiguous. This paper presents an image segmentation algorithm that can effectively deal with images taken at high-solid concentrations. The method segments crystals attached to each other along the mostly related concave points on the contours of crystal blocks. The detailed procedure is introduced with application to crystallization of L-glutamic acid in a hot-stage reactor.

关键词： Crystallization High-solid concentrations Image processing Multi-scale segmentation Watershed segmentation Crystal size distribution

Comparison Study of Constitutive Models for Overconsolidated Clays

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Acta Mechanica Solida Sinica 2020年第1期33卷 98-120页

作者： Z.wan y.P.yao Z.W.Gao Research Institute of Base and Foundation China Academy of Building ResearchBeijing 100013China School of Transportation Science and Engineering Beihang UniversityBeijing 100091China School of Engineering University of GlasgowGlasgow G128QQUK

Widely distributed in natural deposits,the overconsolidated(OC)clays have attracted extensive experimental investigations on their mechanical behaviors,especially in the 1960s and *** on these results,numerous constitutive models have also been *** models generally fall into two categories:one based on the classical plasticity theory and the other the bounding surface(BS)plasticity theory,with the latter being more popular and *** BS concept and the subloading surface(SS)concept are the two major BS plasticity *** features of these two concepts and the representative models based on them are introduced,*** unified hardening(UH)model for OC clays is also based on the BS plasticity theory but distinguishes itself from other models by the integration of the reference yield surface,unified hardening parameter,potential failure stress ratio,arid transformed stress *** is made to the Hvorslev envelop employed in the UH model to improve its capability of describing the behaviors of clays with extremely high overconsolidation ratio in this *** comparison among the BS model,SS model,and UH model is *** shows that all these three models can characterize the fundamental behaviors of OC clays,such as the stress dilatancy,strain softening and attainment of the critical *** UH model with the revised Hvorslev envelop has the fewest parameters which are identical to those of the modified Cam-Clay model.

关键词： Clay Overconsolidation Critical state Bounding surface Subloading surface Unified hardening model

Numerical studies on swirling of internal fire whirls with experimental justifications

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Building Simulation 2021年第5期14卷 1499-1509页

作者： Zheming Gao S.S.Li y.Gao H.y.Hung wan-ki Chow Midea Residential Air Conditioner Division FoshanGuangdongChina College of Aerospace and Civil Engineering Harbin Engineering UniversityHarbinHeilongjiangChina Department of Building Services Engineering The Hong Kong Polytechnic UniversityHunghomKowloonHong KongChina

Numerical studies on internal fire whirls(IFW)generated in a vertical shaft model with a single corner gap were reported in this *** generation of IFW,burning rate of fuel and temperature were studied experimentally *** simulations on medium-scale IFW were carried out using a fully-coupled large eddy simulation incorporating subgrid scale turbulence and a fire source with heat release rates compiled from experimental *** transient flame shape was studied and then simulated numerically by using *** dynamic phenomena of generation and development of IFW were simulated and then compared with experimental *** predicted results were validated by comparing with experimental data,which demonstrated that an IFW can be simulated by Computational Fluid *** results for flame surface,temperature,and flame length agreed well with the experimental *** IFW flame region and intermittent region were longer than those for an ordinary pool *** modified empirical formula for centerline temperature was *** of vertical and tangential velocity in axial and radial directions were also *** vortex core radius was found to be determined by the fuel bed *** field was not measured extensively due to resources *** measured temperature distribution with predictions is acceptable because temperature is related to the heat release rate,air flow and pressure gradient.

关键词： internal fire whirl large eddy simulation vertical structure flame surface

The TGF-β superfamily cytokine Activin-A is induced during autoimmune neuroinflammation and drives pathogenic Th17 cell differentiation

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The TGF-β superfamily cytokine Activin-A is induced during ...

Involuntary Unemployment： An Expository Note

第十四届全国免疫学学术大会

作者： Bing Wu yisong wan UNC at Chapel hill 武汉大学

Th17 cells are known to exert pathogenic and non-pathogenic functions. Although the cytokine transforming growth factor b1(TGF-β1) is instrumental for Th17 cell differentiation, it is dispensable for generation of pathogenic Th17 cells. Here, we examined the T cell-intrinsic role of Activin-A, a TGF-β superfamily member closely related to TGF-β1, in pathogenic Th17 cell differentiation. Activin-A expression was increased in individuals with relapsing-remitting multiple sclerosis and in mice with experimental autoimmune encephalomyelitis. Stimulation with interleukin-6 and Activin-A induced a molecular program that mirrored that of pathogenic Th17 cells and was inhibited by blocking Activin-A signaling. Genetic disruption of Activin-A and its receptor ALK4 in T cells impaired pathogenic Th17 cell differentiation in vitro and in vivo. Mechanistically, extracellular-signal-regulated kinase(ERK) phosphorylation, which was essential for pathogenic Th17 cell differentiation, was suppressed by TGF-β1-ALK5 but not Activin-A-ALK4 signaling. Thus, Activin-A drives pathogenic Th17 cell differentiation, implicating the Activin-A-ALK4-ERK axis as a therapeutic target for Th17 cell-related diseases.

关键词： autoimmune disease multiple sclerosis EAE pathogenic Th17 cells Activin-A ALK4 TGF-β1 ALK5 ERK1/2

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Frontiers of Economics in China-Selected Publications from Chinese Universities 2018年第1期13卷 83-92页

作者： Henry y. wan Jr. Department of Economics Comell University Ithaca NY 14853 USA

This note is an effort to view the research program of Brecher and his co-workers to deploy tax incentives against involuntary unemployment in the broader context; on both the equity-efficiency trade-off in political ... 详细信息

关键词： involuntary unemployment efficiency wage wage rigidity