简介：ToobservepotentialeffectoftheengineeredbonemarrowstromalcelllineQXMSC1secretingIL-6(QXMSCIL-6)onacceleratingimmnunereconstitutioninsyngeneicbonemarrowtransplantationinmice,QXMSC1wastransfectedwiththeeukaryocyticexpressionvectorpcDNAIL-6,whichcontainedhIL-6cDNAbyliposome-mediatedgenetransfectingtechnique.G418-resistanceclonewasselectedbylimitingdilution.ThehighestsecretingclonewasselectedbyELISAassayandusedinanimalexperiments.Therecipientmice(BALB/c)werelethallyirradiatedandcotransplantedsyngeneicbonemarrow(10^7/mice)andtheQXMSCIIL-6(5×10^5/mice).LymphocyteproliferationinducedbyConAandLPS,helperTlymphocyteprecursor(HTLp),cytotoxicTlymphocyteprecursor(CTLp),plaque-formingcell(PFC),delayedtypehypersensitivity(DTH)wereexamined30,60daysinposttransplantationrespectively.TheresultsshowedthatlymphocytesproliferationtoConAandLPS,HTLp,CTLpincreased,DTHandPFCwereimprovedbycograftedstromalcellsQXMSCIIL-6on30,60daysafterBMT.TheseresultsdemonstratedthatthebonemarrowstromalcelllineQXMSC1IL-6transfectedwithIL-6(QXMSC11L-6)acceleratedimmnunereconstitutioninsyngeneicbonemarrowtransplantation.

简介：Survivalratesformetastaticlungcancer,includingnon-smallcelllungcancer(NSCLC)andsmallcelllungcancer(SCLC),arepoorwith5-yearsurvivalsoflessthan5%.Theimmunesystemhasanintricateandcomplexrelationshipwithtumorigenesis;agroundswellofresearchontheimmunesystemisleadingtogreaterunderstandingofhowcancerprogressesandpresentingnewwaystohaltdiseaseprogress.Duetotheextraordinarypoweroftheimmunesystem—withitscapacityformemory,exquisitespecificityandcentralanduniversalroleinhumanbiology—immunotherapyhasthepotentialtoachievecomplete,long-lastingremissionsandcures,withfewsideeffectsforanycancerpatient,regardlessofcancertype.Asaresult,arangeofcancertherapiesareunderdevelopmentthatworkbyturningourownimmunecellsagainsttumors.Howeverdeeperunderstandingofthecomplexityofimmunomodulationbytumorsiskeytothedevelopmentofeffectiveimmunotherapies,especiallyinlungcancer.

简介：Recombinanthumanprolactin(rhPRL)wasadministeredtohuPBL-SCIDmicetodetermineitseffectsonhumanimmunologicreconsfitutionandfunction.ThehuPBL-SCIDmiceweregiven10μgI.p.InjectionofrhPRLeveryotherdayforatotalof10injectionsafterhuPBLweretransferred.TheresultsdemonstratedthatrhPRLimprovedtheengraftmentoflymphocytesintothymus,lymphnodesandspleens,showingthatthecellularitiesoftheseorgansincreasedalthoughthecellularitiestendedtovarydependingonthedonor.TheamountsofhumanTcells(HLA-ABC+/CD3+)increasedgreatlyinthymus(14.2folds),spleen(4.16folds)andlymphnodes(40.18folds)afterrhPRLinjections.TheamountsofhumanBcells(HLA-ABC+/CD19+)alsoincreasedgreatlyinlymphnodes(42.5folds)andspleen(5.78folds).ThelymphnodecellsfromtherhPRL-treatedhuPBL-SCIDmiceweremoresensitivetoPHAstimulation([3H]thymidineincorporation).ThesupernatantofPHA-stimulatedPBLfromrhPRL-treatedhuPBL/SCIDchimerismcontainedmorecytokines(IFN-γandIL-2).Thenaturalcytotoxicityagainsthumansensitivetargetcells,K562cells,fromspleenandbonemarrowofhPBL/SCIDchimerismwassignificantlyenhancedbyrhPRLadministration.ThelymphnodecellswerestimulatedwithLPSinvitrofor3daysandthelymphocytesfromtherhPRL-treatedhuPBL-SCIDmiceweremoresensitivetomitogenstimulation.BothserumtotalIgGlevelandIgMlevelofrhPRL-treatedhuPBL/SCIDchimerismwereincreased,andevenwithoutDT-rechallengethebaselineofDT-specificIgGwaselevatedafterrhPRLtreatmentinhuPBL-SCIDmice.Thus,rhPRLstimulationpromotesreconstitutionofhumanimmunesysteminhuPBL-SCIDmice.

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简介：Exosomes,secretedbymanylivecells,aresmallnon-cellvesicleswithnanoparticle-gradesize.Inadditiontotheoriginalfunctionofdiscardingtheuselessfulmembranemolecules,exosomesareinvolvedinarangeofimmunoregulatoryfunctions.Dendriticcell-derivedexosomesandtumor-derivedexosomesarethebestcharacterizedvesicleswithpotentantitumoreffectbyefficienflyinducingimmuneresponse.Down-regtdationofimmuneresponseorinductionofimmunetoleranceisanotherinterestingfunctionofexosomes，Furtherfunctionalstudiesoftheexosomeswillshedlightontheapplicationofexosomes。

简介：尽管免疫系统拥有工具对癌症作出回应，它经常没能控制恶意的传播。尽管如此，装备内长的免疫释放强壮的antitumor回答比常规治疗有重要优点。这评论探索一些可得到的选择完成这，在有刺激免疫系统并且授权更强壮的antitumor回答的肿瘤抗原的种痘上集中第一。我们然后比较并且形成对照声发有用淋巴细胞转移的T的采纳治疗的记录得好的药品潜力的种痘的有限临床的成功。最后，我们用与受体一起利用allogeneicT房间全部剧目的房间受体(TCR)基因转移策略为定义MHC/peptide联合在vitro选择了的T加亮新奇途径，作为癌症的抗原特定的基因治疗的一个基础。

简介：AbstractMedulloblastoma is the most common primary pediatric malignancy of the central nervous system. Recurrent and refractory patients account for approximately 30% of them. Immune cells are an important component of the brain tumor microenvironment, including tumor-associated macrophages, T lymphocytes, natural killer cells, dendritic cells, neutrophils and B lymphocytes. Understanding how they behave and interact is important in the investigation of the onset and progression of medulloblastoma. Here, we overview the features and recent advances of each component of immune cells in medulloblastoma. Meanwhile, immunotherapy is a promising but also challenging treatment strategy for medulloblastoma. At present, there are a growing number of immunotherapeutic approaches under investigation including immune checkpoint inhibitors, oncolytic viruses, cancer vaccines, chimeric antigen receptor T cell therapies, and natural killer cells in recurrent and refractory medulloblastoma patients.

简介：幼芽的中心kinases(GCK)参予需要包括apoptosis，房间增长，极性和移植调整细胞的函数的许多发信号的小径。最近的研究证明了GCK是在适应、天生的有免疫力的规定的参加者。然而，微分激活和GCK的规章的机制，以及在上游、下游的发信号的分子，尚待充分被定义。它仍然保持未解决是否并且怎么GCK可以有存在的串音表明小径。这评论在与免疫系统相关的GCK的研究强调进步。

简介：Modulationbybalancingactivatingandinhibitoryreceptorsconstitutesanimportantmechanismforregulatingimmuneresponses.Cellsthatareactivatedfollowingligationofreceptorsbearingimmunoreceptortyrosine-basedactivationmotifs(ITAMs)canbenegativelyregulatedbyotherreceptorsbearingimmunoreceptortyrosine-basedinhibitionmotifs(ITIMs).Humanmastcells(MCs)arethemajoreffectorcellsoftypeIhypersensitivityandimportantparticipantsinanumberofdiseaseprocesses.Antigen-mediatedaggregationofIgEboundtoitshigh-affinityreceptoronMCsinitiatesacomplexseriesofbiochemicaleventsleadingtoMCactivation.WithgreatdetaileddescriptionandanalysisofseveralinhibitoryreceptorsonhumanMCs,acentralparadigmofnegativeregulationofhumanMCactivationbythesereceptorshasemerged.Cellular&MolecularImmunology.2004;1(6):408-415.

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简介：Enteralnutritionhasbeenstronglyrecommendedbymajorscientificsocietiesforthenutritionalmanagementofpatientswithacutepancreatitis.Providingsevereacutepancreatitispatientswithenteralnutritionwithinthefirst24-48hofhospitaladmissioncanhelpimproveoutcomescomparedtoparenteralnutritionandnofeeding.Newresearchisfocusinginonwhenandwhattofeedtobestimproveoutcomesforacutepancreatitispatients.Earlyenteralnutritionhavethepotentialtomodulatetheimmuneresponses.Despitethisconsistentevidenceofearlyenteralnutritioninpatientswithacutepancreatitis,clinicalpracticecontinuestovaryduetoindividualclinicianpreference.Achievingtheimmunemodulatingeffectsofenteralnutritionheavilydependonproperplacementofthefeedingtubeandmanaginganytubefeedingassociatedcomplications.Thecurrentarticlereviewstheimmunemodulatingeffectsofenteralnutritionandpro-andprebioticsandsuggestssomepracticaltoolsthathelpimprovethepatientadherenceandtolerancetothetubefeeding.Properselectionofthetypeofthetube,closemonitoringofthetubeforitsplacement,patencyandsecuringitsproperplacementandroutinecheckingthegastricresidualvolumecouldallhelpimprovetheoutcome.Usingpeptide-basedandhighmediumchaintriglyceridesfeedingformulashelpimprovingfeedingtolerance.

简介：在血流动的Receptor-ligand相互作用是关键的作为煽动性的串联，血小板血栓，以及肿瘤转移开始生物过程。为了调停，房间粘附，交往的受体和ligands必须被抛锚到二个房间或一个房间和一个基础的二apposing表面上，即，二维(2D)绑定，与在到受体的液体阶段的可溶的ligand的绑定不同，三维(3D)有约束力。当众多的工作在免疫系统集中于receptor-ligand相互作用的3D动力学时，2D动力学和它的规定少些被理解，自从没有理论框架和试验性的试金被建立了直到1993。不仅分子的结构统治在血流动的力量也调整的2D绑定动力学，而是shear房间粘附由交往的受体和ligands调停了。这里，我们在2D绑定和规定提供了当前的进步的概述。理论框架，试验性的大小，运动的率和有约束力的亲密关系的相关问题，和力量规定，被讨论。

简介：Deareditors,Neurodegenerativediseasesarenowassociatedwiththeglobalobesityanddiabetesepidemicinthedevelopinganddevelopedworld.Neurodegenerativediseasesareaheterogeneousgroupofdisorderswithcomplexfactorssuchasneurohumoral,endocrineandenvironmentalfactorsinvolvedininductionoftheseneurodegenerativediseases.Thefutureofscienceandmedicineinneurodegenerativediseasesisnowdependentonnutritionalgenomicswithinsulinresistanceamajorfactorintheinductionofneurodegenerativediseases.Nutritionalgenomicsnowinvolvestheanti-aginggeneSirtuin1(Sirt1)thatisimportanttothepreventionofinsulinresistancewithitscriticalinvolvementintheimmunesystem(Martins,2018a,b).Sirt1inactivationleadstotoxicimmunereactionsconnectedtotheaccelerationofneurondeathinvariouscommunities.Appetitecontrolwithrelevancetoimmunometabolismhasbecomeofcriticalimportancetothetreatmentofneurodegeneration(Figure1).NutritionaldietsactivatetheheatshockgeneSirt1topreventtheincreaseinheatshockproteinsconnectedtoautoimmunedisease,mitophagy(Martins,2018a,b)andirreversibleprogrammedcelldeathinglobalpopulations(Figure1).

简介：AbstractHidradenitis suppurativa (HS) is a chronic, inflammatory skin condition that poses a significant diagnostic and therapeutic challenge for clinicians, as the underlying etiology and pathogenesis remains unclear. The host of genetic mutations and immune dysfunction has been identified to be involved in the pathogenesis of HS during recent years. These genetic defects, including monogenetic mutations altering subunits of γ-secretase, a protease that functions through Notch signaling to maintain skin appendages, promote epithelial stability, suppress/terminate innate immune responses (ie, Toll-receptors), further have the propensity to induce aberrant cytokine responses that create to a proinflammatory environment, consequently induce hyperkeratosis and promote expression of pro-inflammatory, locally destructive matrix metalloproteinases. Cytokine-driven inflammation propagates the disease state of HS and contributes to the formation of painful subcutaneous nodules, abscesses, and eventually, fistulas and draining sinus tracts. A closer look at genetic mutations linked to the disease may explain the immune perturbations seen in HS. An understanding of the immune cells and inflammatory markers expressed in affected individuals provides insight into disease pathogenesis and can help identify therapeutic targets.

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简介：氮的氧化物(没有)作为一个immunoregulatory分子，主要取决于S-nitrosylation，充当执行它的规定和信号transduction的一个万用的播放器因为施加它有免疫力的房间的多功能和pleiotropy.Apoptosis是结合的复杂进程取决于综合多样的内长、外长的信号和函数在免疫系统支撑动态平衡的积极/否定的选择。这里，不在apoptosis取决于它的集中的双角色被考察，在在apoptotic过程的一个开关模式上面繁殖。从apoptosis死亡的不同开关的后面的评价，开始GSNO的thymocyteapoptosis和NOS-GSNOR双控制的检查点(早荧光点)的新发现是highlighted.Moreover，S-nitrosylation/denitrosylation，作为一个氧化还原作用切换，逻辑地来临到新陈代谢本身和进一步的存取的网络整个的neuroendicrine-immune-free激进分子网络。而且，主人防卫调停了由不在病原体上，经由蛋白质，S-nitrosylation也被讨论。

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简介：AbstractWith the increasing use of immune checkpoint inhibitors (ICI) including anti-cytotoxic T lymphocyte associated antigen-4 (CTLA-4) and anti-programmed cell death-1 (PD-1) in cancers, ICI-induced type 1 diabetes has been reported throughout the world. In this review, we aim to summarize the characteristics of this disease and discuss the mechanism of it. As an immune-related adverse event, type 1 diabetes developed after the administration of anti-PD-1 or anti-PD-ligand 1 (PD-L1) in the combination with or without anti-CTLA-4. It usually presented with acute onset, and 62.1% of the reported cases had diabetic ketoacidosis. Only a third of them had positive autoantibodies associated with type 1 diabetes. Susceptible HLA genotypes might be associated. T-cell-stimulation by blocking of the interaction of PD-1 and PD-L1 in pancreatic β cells was the main mechanism involved in the pathology. Insulin was the only effective treatment of ICI-induced type 1 diabetes. In conclusions, ICI-induced type 1 diabetes is a potentially life-threating adverse event after the immunotherapy of cancers. Screening and early recognition is important. Further investigation of the mechanism may help to better understand the pathology of type 1 diabetes.

简介：Objective:Todetecttheexistenceofimmunetoleranceinducedbygamma-rayirradiation.Methods:Peritonealcellswereharvestedfrommicesubjectedto5Gy60Cogamma-raytotalbodyirradiationat3d,7d,15dand30d,thentheircounts,morphologicalchangesandIL-12geneexpressionwereinvestigated.Results:Afterirradiation,theperitonealcellsweresharplyreduced,thecellmorphologyshiftedfromround-liketopolymorphicandfusiformwithsomeprocesses,expressionofIL-12p35wasseriouslysuppressed,whilethatofIL-12p40greatlyenhanced.Conclusion:Ourdatahighlysuggestthatthegamma-rayirradiationcouldpotentiallyinducedendriticcell(DC)commitmentandimmunetolerance.

简介：NF-κBisatranscriptionfactorofeukaryote,fivemembersofwhosefamilyinmammalsandthreeindrosophila.TranscriptionfactorsoftheNF-κfamilyareactivatedinresponsetosignalsthatleadtocellgrowth,differentiation,apoptosisandotherevents.NF-κBtakespartinexpressionofnumerouscytokinesandadhesionmoleculeswhicharecriticalelementsinvolvedintheregulationofimmuneresponses.Inthisreview,wefocusonourcurrentunderstandingofNF-κBsignalpathwayanditsroleintheinnateandadaptiveimmuneresponsesinwhichthesetranscriptionfactorshaveakeyregulatoryfunction.Furthermorewereviewwhatiscurrentlyknownabouttheireffectsassociatedwithapoptosis.Cellular&MolecularImmunology.2004;1(5):343-350.