INTRODUCTION:Interleukin-33 (IL-33) is a damage-associated alarmin that may have a profound effect on systemic inflammation. Dendritic cells (DCs) are critically involved in sepsis progression, but the precise regulation of DC function by IL-33 remains unresolved. OBJECTIVES:This study explored the role of the IL-33 signaling axis in DC activation during sepsis. METHODS:The role of IL-33 was investigated using an in vitro DC system and a cecal ligation and puncture-induced sepsis model in wild-type and interleukin-1 receptor-like 1 (IL-1RL1)-deficient mice. Downstream mechanisms were dissected through proteomic analysis, Western blotting, and genetic ablation. Validation was performed using mice deficient in reticulophagy regulator 1 (RETREG1) and activating transcription factor 6 (ATF6), as well as with the inhibitor of calcium/calmodulin-dependent kinase II (CaMKII). RESULTS:IL-33 stimulation potently enhanced DC function in an IL-1RL1-dependent manner. IL-33 promoted RETREG1-mediated reticulophagy, a process essential for DC activation, as DCs from Retreg1-/- mice showed markedly attenuated activation responses. Mechanistically, IL-33 induced the nuclear translocation of ATF6, a transcription factor implicated in RETREG1 regulation. Concurrently, IL-33 activated CaMKII, which was associated with increased RETREG1 phosphorylation, thereby potentiating RETREG1-driven reticulophagy. CONCLUSION:Our findings unveil a novel pathway wherein IL-33 orchestrates DC immune function during early sepsis through a dual mechanism-transcriptional upregulation and functional potentiation of RETREG1. Modulation of IL-33/RETREG1-mediated reticulophagy may inform therapeutic development for septic complications.

Dendritic cells (DCs) are crucial antigen-presenting cells that mediate the interplay between innate and adaptive immunity during lethal infections. Here, we report the key role of reticulophagy regulator 1 (RETREG1), a selective autophagy receptor, in maintaining DC maturation and function in the early stage of sepsis. Mechanistically, activating transcription factor 6 (ATF6) acts as a direct transcription factor regulating RETREG1 expression in response to bacterial lipopolysaccharide-induced endoplasmic reticulum (ER) stress. RETREG1-mediated reticulophagy reduces excessive ER stress via the eukaryotic translation initiation factor 2 alpha kinase 3 (EIF2AK3) signaling pathway and inhibits membrane-associated RING-CH-type finger 8 (MARCH8)-dependent major histocompatibility complex class II (MHC-II) ubiquitination to maintain antigen presentation in DCs. Consequently, Cd11ccreRetreg1fl/fl, Retreg1-/-, and Atf6-/- mice exhibit impaired DC function, leading to immunosuppression and multiple organ failure in experimental sepsis. Exploration of samples from septic patients, combined with single-cell bioinformatics analysis, further suggests that a deficit in reticulophagy in DCs is associated with the development of human sepsis.

Background:Sepsis is a life-threatening condition characterized by profound immune dysregulation and organ dysfunction. The functional impairment of dendritic cells (DCs) in septic patients is well-documented and contributes significantly to sepsis-induced immunosuppression; yet the underlying mechanisms remain poorly understood. Tripartite motif 13 (TRIM13) has been identified as an immune regulator with predominantly suppressive effects. Here, we aimed to investigate the potential role of TRIM13 restriction in promoting the DC-mediated immune response during sepsis. Methods:Splenic DCs were isolated from wild-type (WT) and DC-specific Trim13 conditional knockout (Trim13 cKO) mice post-cecum ligation and puncture (CLP). These cells were subsequently analyzed by proteomics, immunoblotting, flow cytometry, and transmission electron microscopy (TEM). DC2.4 cells were infected with either Trim13 shRNA or a Trim13 overexpression lentiviral vector and treated with different pharmacological inhibitors. Protein interactions were examined via coimmunoprecipitation (Co-IP) and confocal microscopy. Cytokine levels were measured by enzyme-linked immunosorbent assay (ELISA), and organ lesions were assessed through hematoxylin and eosin (H&E) staining, immunohistochemistry (IHC) for CD45, and TUNEL assays. Results:TRIM13 expression was rapidly upregulated in DCs following septic challenge. Deletion of TRIM13 in DCs disrupted the endoplasmic reticulum (ER)-associated degradation (ERAD) and ER-selective autophagy (ER-phagy)-mediated degradation of the stimulator of interferon genes (STING), leading to sustained STING activation and enhanced DC function. STING signaling promoted the p-IRF3 nuclear translocation, NLRP3 inflammasome priming, and transient DC pyroptosis, thereby exacerbating hyperinflammation in the acute phase of sepsis. Over the longer term, prolonged STING signaling inhibited DCs from adopting the immunosuppressive phenotype and promoting the DC-mediated immune response. Ultimately, TRIM13 deficiency in DCs ameliorated sepsis-induced immunosuppression, preserved organ function in the late phase of sepsis, and reduced overall mortality in septic mice. Conclusions:TRIM13 acts as a key negative regulator of DC function during sepsis. Restricting TRIM13 sustains DC immunostimulatory property, counteracts sepsis-induced immunosuppression, and improves survival outcomes. These findings highlight TRIM13 as a potential therapeutic target for sepsis management.

Sepsis, a life-threatening health issue, lacks effective medicine targeting the septic response. In China, treatment combining the intravenous herbal medicine XueBiJing with conventional procedures reduces the 28-day mortality of critically ill patients by modulating septic response. In this study, we identified the combined active constituents that are responsible for the XueBiJing’s anti-sepsis action. Sepsis was induced in rats by cecal ligation and puncture (CLP). The compounds were identified based on their systemic exposure levels and anti-sepsis activities in CLP rats that were given an intravenous bolus dose of XueBiJing. Furthermore, the identified compounds in combination were assessed, by comparing with XueBiJing, for levels of primary therapeutic outcome, pharmacokinetic equivalence, and pharmacokinetic compatibility. We showed that a total of 12 XueBiJing compounds, unchanged or metabolized, circulated with significant systemic exposure in CLP rats that received XueBiJing. Among these compounds, hydroxysafflor yellow A, paeoniflorin, oxypaeoniflorin, albiflorin, senkyunolide I, and tanshinol displayed significant anti-sepsis activities, which involved regulating immune responses, inhibiting excessive inflammation, modulating hemostasis, and improving organ function. A combination of the six compounds, with the same respective doses as in XueBiJing, displayed percentage survival and systemic exposure in CLP rats similar to those by XueBiJing. Both the combination and XueBiJing showed high degrees of pharmacokinetic compatibility regarding interactions among the six active compounds and influences of other circulating XueBiJing compounds. The identification of XueBiJing’s pharmacologically significant constituents supports the medicine’s anti-sepsis use and provides insights into a polypharmacology-based approach to develop medicines for effective sepsis management.

Megakaryocytes are traditionally recognized as cells responsible for platelet production. However, beyond their role in thrombopoiesis, megakaryocytes also participate in inflammatory responses and regulate immune system functions. Sepsis, characterized by life-threatening organ dysfunction due to a dysregulated response to infection, prominently features coagulopathy, severe inflammation, and immune dysfunction as key pathophysiological aspects. Given the diverse functions of megakaryocytes, we explore their roles in coagulation in the context of sepsis, and also in inflammatory and immune regulation. We try to infer future research directions and potential strategies for sepsis prevention and treatment based on the properties of megakaryocytes. The purpose of this review is to both highlight and provide an update on the functions of megakaryocytes and pathophysiological changes in sepsis. Specific emphasis is given to the role of megakaryocytes in sepsis, which suggests value of future research and clinical application.

Interleukin (IL)- 33, a nuclear factor and pleiotropic cytokine of the IL-1 family, is gaining attention owing to its important role in chronic inflammatory and autoimmune diseases. This review extends our knowledge of the effects exerted by IL-33 on target cells by binding to its specific receptor serum stimulation-2 (ST2). Depending on the tissue context, IL-33 performs multiple functions encompassing host defence, immune response, initiation and amplification of inflammation, tissue repair, and homeostasis. The levels and activity of IL-33 in the body are controlled by complex IL-33-targeting regulatory pathways. The unique temporal and spatial expression patterns of IL-33 are associated with host homeostasis and the development of immune and inflammatory disorders. Therefore, understanding the origin, function, and processes of IL-33 under various conditions is crucial. This review summarises the regulatory mechanisms underlying the IL-33/ST2 signalling axis and its potential role and clinical significance in immune and inflammatory diseases, and discusses the current complex and conflicting findings related to IL-33 in host responses.

目的 初步观察脓毒症小鼠脾脏树突状细胞(DC)焦亡情况及其与炎性因子水平、DC免疫功能的相关性.方法 70只BALB/c小鼠随机分为假手术组(n=20)、脓毒症模型组(CLP组,n=30)与胱天蛋白酶(CASP)-1抑制剂干预组(CLP+YVAD组,n=20),CLP组和CLP+YVAD组按术后不同时间点分为CLP 12 h组、CLP 24 h组、CLP 48 h组、CLP 72 h组及CLP+YVAD 24 h组、CLP+YVAD 72 h组.所有小鼠于术后预定时间眼眶取血、处死并取脾脏组织.流式细胞仪测定脾脏DC焦亡率及表面标志物(CD80、CD86、MHC-Ⅱ)表达水平,激光共聚焦显微镜观察CASP-1在小鼠脾脏DC中的活化情况,Western blotting检测DC中CASP-1的表达情况,ELISA法检测血清中肿瘤坏死因子(TNF)-α、白细胞介素(IL)-12、IL-1β、IL-6浓度;观察CLP术后小鼠死亡情况.提取BALB/c小鼠T细胞与各组小鼠脾脏DC共培养,采用流式细胞仪测定T细胞增殖率,ELISA法检测共培养上清中γ干扰素(IFN-γ)、IL-4、IL-10浓度.结果 与假手术组比较,DC焦亡率在CLP术后12 h升高(P<0.05),于24 h达高峰(P<0.01),随后呈下降趋势,至72 h仍高于假手术组(P<0.01).激光共聚焦显微镜观察显示,CLP术后小鼠脾脏DC CASP-1活化明显.Western blotting检测结果显示,DC中焦亡蛋白CASP-1表达在脓毒症早期(12 h和24 h)较假手术组明显上调(P<0.01).而给予CASP-1特异性抑制剂Ac-YVAD-cmk后,CLP+YVAD 24 h组DC焦亡率较CLP 24 h组下降(P<0.01),CLP+YVAD 72 h组DC表面标志物CD80、MHC-Ⅱ表达水平较CLP 72 h组上调(P<0.01),术后7 d小鼠生存率提高(P<0.01).ELISA法检测结果显示,CLP小鼠血清TNF-α、IL-12、IL-1β和IL-6浓度在脓毒症早期(24 h)和后期(72 h)均较假手术组明显升高(P<0.01),而CLP+YVAD组血清内上述因子浓度明显下降(P<0.01).共培养实验结果显示,与DC-CLP 24 h组比较,DC-CLP+YVAD 24 h组T细胞增殖率明显增高(P<0.01),共培养上清中IFN-γ水平下降,而IL-4、IL-10水平上升(P<0.01).结论 DC焦亡在脓毒症早期启动并持续存在,可能是脓毒症状态下炎性因子水平异常增高和DC免疫功能抑制的病理生理机制之一,且与脓毒症预后不良相关.

脓毒症是一个全球性重大健康问题,是全球重症监护病房(ICU)患者死亡的主要原因,严重威胁人类可持续发展和社会的不断进步. 临床资料表明,每年发生的5 000 万脓毒症病例中约有1 100 万人死亡,约占全球总死亡人数的 20％ [1]. 近年来,对全国44 家医院ICU脓毒症患者开展了流行病学调查,结果显示,国内脓毒症患者 90 天病死率为35.5％,发生脓毒性休克者病死率高达51. 94％ [2].目前,世界卫生组织(WHO)将脓毒症确定为对患者安全和公共健康的重大威胁,脓毒症诊断、预防、治疗和管理均亟待加强. 随着对免疫反应调控途径及细胞损伤机制研究的逐步深入,对脓毒症病理过程中免疫障碍关键作用的认知逐步加深;但用于脓毒症临床诊断和治疗实践的确切措施十分有限,仍缺乏针对免疫功能障碍核心发病环节的有效治疗方法,脓毒症免疫调理策略的临床转化应用依然任重而道远.

目的 探究脓毒症状态下老年小鼠脾脏树突状细胞(dendritic cell,DC)功能状态的异常改变及其与高尔基体应激反应和自噬反应的内在联系.方法 不同年龄小鼠(青年鼠 8周龄,老年鼠18 月龄)分别随机分为假手术组与脓毒症模型组(CLP组)(n =4).CLP组小鼠于术后24h处死并取脾脏组织.采用免疫磁珠法分离纯化脾脏DC,流式细胞术检测各组DC表面标志物及共刺激分子(CD80、CD86、MHC-Ⅱ)表达水平.分离纯化不同年龄小鼠脾脏DC,各自分为空白对照组、LPS刺激组(1 μg/mL)(n =4).免疫印迹法检测各组细胞高尔基体应激反应相关蛋白——高尔基体磷蛋白 3(Golgi phosphoprotein 3,GOLPH3)、高尔基体重组堆积蛋白 2(Golgi reassembly stacking protein of 55 kDa,GRASP55)以及高尔基体自噬相关蛋白高尔基体蛋白亚家族A成员2(Golgi matrix protein,GM130)、微管相关蛋白 1A和 1B(microtubule-associated proteins 1A and 1B,MAP1LC3B)表达水平.激光共聚焦显微镜检测高尔基体红色荧光探针(Golgi-tracker Red)在各空白对照组中的显示情况.进一步应用抑制高尔基体蛋白转运的莫能菌素(monensin,MON)(1 μg/mL)预处理,检测扰乱高尔基体稳态对小鼠DC功能分化的影响.结果 与青年小鼠比较,老年脓毒症模型小鼠脾脏DC活化障碍显著.CLP术后 24h老年小鼠脾脏DC表面标志分子CD80、CD86、MHC-Ⅱ表达升高水平明显低于青年小鼠(P<0.05).对比健康小鼠脾脏DC胞内高尔基体的结构功能状态发现,与青年小鼠比较,老年DC胞内高尔基体结构蛋白GRASP55、GM130 呈高表达(P<0.001),提示高尔基体结构肿胀;高尔基体外膜蛋白GOLPH3表达减弱(P<0.001),提示蛋白修饰及转运功能低下.分离提取不同年龄小鼠脾脏DC进行体外培养并给予LPS刺激,发现脓毒症老年小鼠DC胞内高尔基体应激反应增强、自噬明显,与DC功能障碍密切相关.给予MON抑制高尔基体蛋白转运,观察到青年、老年小鼠DC胞内高尔基体均发生显著应激与自噬反应,青年小鼠DC免疫功能活化障碍,老年小鼠功能障碍则更为显著.结论 老年小鼠DC中高尔基体结构肿胀且功能受损,造成DC免疫功能活化障碍,与老年脓毒症免疫抑制密切相关.

Interleukin (IL)-33, a nuclear factor and a cytokine of the IL-1 family, has received a lot of attention in recent years because of its important role in chronic inflammatory and autoimmune diseases. It appears to be critically involved in the regulation of various physiological processes by influencing a wide range of immune cells. Previous reports and studies have primarily focused on the effects of IL-33 on traditional target cells, such as mast cells and type 2 innate lymphocytes. Dendritic cells (DC) are the most functionally specialized antigenpresenting cells that have been discovered to date. It has been demonstrated that IL-33 can activate DC via its specific receptor serum stimulation-2 (ST2), thereby regulating the host immune response and playing key roles in the pathogenesis of occurrence and progression of various diseases. The immune regulation of DC by IL-33 mainly involves signal pathways, such as NF-kappa B, p38 MAPK, and STAT1/3, in turn mediating the maturation, differentiation, and inflammatory response of DC. In addition, DC is an important source of the secretion of IL-33, which enhances the immune reaction and Th2 response through a positive feedback amplification loop. IL-33 activated DCs can promote tumor immunity and resist pathogen invasion, and also participate in the development of autoimmune and inflammatory diseases. This paper reviews the potential role and underlying mechanism of IL-33 in regulating DC immune response in order to provide a foundation for further research into its immune function and modulatory pathway in diseases.

Aims Our objective was to explore whether the accuracy of the transitional zone index (TZI) for outflow tract ventricular arrhythmias (OT-VAs) origin is affected by cardiac rotation and the additive value of interventricular septum angle (IVSa) obtained from coronary computed tomography angiography (CCTA). Methods Standard 12-lead ECGs of OT-VAs with inferior axis in consecutive patients undergoing both CCTA examination and successful ablation were retrospectively analyzed. The IVSa was defined as an angle between the long axis of IVS and sagittal axis of the body from CCTA. Results 64 patients (31 men; mean age 54.2 +/- 11.6 years) were enrolled. The OT-VAs exhibited right ventricular outflow tract origin in 46 (71.9%) patients and 36 (78.3%) were diagnosed correctly by TZI. The left ventricular outflow tract origin OT-VAs was observed in 18 (28.1%) patients and 16 (88.9%) were diagnosed correctly by TZI. The patients were then divided into TZI correct group (n = 52) and TZI incorrect group (n = 12). In the TZI incorrect group, 11/12 (91.7%) cases were R/S transition in lead V3 with the TZ score during premature ventricular contractions [2.8(2.5-3.4)], and the TZI between -1.5 and 0. The IVSa was significantly larger in the TZI incorrect group than correct group (52.0 +/- 6.9 degrees vs. 39.0 +/- 6.1 degrees; p < .0001). The IVSa >= 46 degrees predicted TZI incorrect with 92% sensitivity, 94% specificity, and 94% accuracy. Conclusion The IVSa is a novel cardiac rotation index that reliably improves TZI to differentiate the OT-VAs origin, especially for the OT-VAs with lead V3 R/S transition.

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Sepsis-induced circulatory and cardiac dysfunction is associated with high mortality rates. Mitophagy, a specific form of autophagy, is excessively activated in lipopolysaccharide-induced myocardial injury. The present study investigated whether aldehyde dehydrogenase 2 (ALDH2) regulates mitophagy in sepsis-induced myocardial dysfunction. After lipopolysaccharide administration, cardiac dysfunction, inflammatory cell infiltration, biochemical indicators of myocardial cell injury, and cardiomyocyte apoptosis were ameliorated in mice by ALDH2 activation or overexpression. In contrast, cardiac dysfunction and cardiomyocyte apoptosis were exacerbated in mice followed ALDH2 inhibition. Moreover, ALDH2 activation or overexpression regulated mitophagy by suppressing the expression of phosphatase and tensin homolog-induced putative kinase 1 (PINK1)/Parkin, by preventing the accumulation of 4-hydroxy-trans-nonenal. Conversely, ALDH2 inhibition promoted the expression of LC3B by increasing 4-hydroxy-trans-2-nonenal accumulation. Consequently, ALDH2 may protect the heart from lipopolysaccharide-induced injury by suppressing PINK1/Parkin-dependent mitophagy.

Sepsis is caused by various pathogens and toxic factors, which can lead to multiple organ dysfunction. The underlying mechanism of sepsis appears to be complex, involving epigenetic reprogramming, metabolic failure, immune dysfunction, neuroendocrine system disorders, coagulation abnormalities, tissue or organ failure, and many other scientific issues. With our deep understanding of the host reaction and development of sepsis, it is of great significance to explore predicative markers and therapeutic targets according to the atypical characteristics of sepsis, thereby contributing to the reduction of morbidity and mortality of sepsis.

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Sestrin2 (SESN2), a highly evolutionarily conserved protein, is critically involved in the cellular response to various stresses and has been confirmed to maintain the homeostasis of the internal environment. However, the potential effects of SESN2 in regulating dendritic cells (DCs) pyroptosis in the context of sepsis and the related mechanisms are poorly characterized. In this study, we found that SESN2 was capable of decreasing gasdermin D (GSDMD)-dependent pyroptosis of splenic DCs by inhibiting endoplasmic reticulum (ER) stress (ERS)-related nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3)-mediated ASC pyroptosome formation and caspase-1 (CASP-1) activation. Furthermore, SESN2 deficiency induced NLRP3/ASC/CASP-1-dependent pyroptosis and the production of proinflammatory cytokines by exacerbating the PERK-ATF4-CHOP signaling pathway, resulting in an increase in the mortality of septic mice, which was reversed by inhibiting ERS. These findings suggest that SESN2 appears to be essential for inhibiting NLRP3 inflammasome hyperactivation, reducing CASP-1-dependent pyroptosis, and improving sepsis outcomes through stabilization of the ER. The present study might have important implications for exploration of novel potential therapeutic targets for the treatment of sepsis complications.

Type Ⅱ innate lymphoid cell (ILC2), a newly discovered important type of inherent immune cells closely related to T lymphocytes, has a significant regulatory impact on T lymphocytes. Many studies have demonstrated that ILC2 can effectively induce the differentiation of CD4+ T cells to helper T cell (Th)2, thereby contributing to the modulation of host immune homeostasis. In the present paper, we would like to review the update of possible effects of ILC2 on Th2 differentiation and its role in immunity diseases. DOI: 10.11855/j.issn.0577-7402.2021.01.12

Sestrin2 (SESN2) is a highly evolutionary conserved protein and involved in different cellular responses to various stresses. However, the potential function of SESN2 in immune system remains unclear. The present study was designed to test whether dendritic cells (DCs) could express SESN2, and investigate the underlying molecular mechanism as well as its potential significance. Herein, we firstly reported that SESN2 was expressed in DCs after high mobility group box-1 protein (HMGB1) stimulation and the apoptosis of DCs was obviously increased when SESN2 gene silenced by siRNA. Cells undergone SESN2-knockdown promoted endoplasmic reticulum (ER) stress (ERS)-related cell death, markedly exacerbated ER disruption as well as the formation of dilated and aggregated structures, and they significantly aggravated the extent of ERS response. Conversely, overexpressing SESN2 DCs markedly decreased apoptotic rates and attenuated HMGB1-induced ER morphology fragment together with inhibition of ERS-related protein translation. Furthermore, sesn2 −/− -deficient mice manifested increased DC apoptosis and aggravated ERS extent in septic model. These results indicate that SESN2 appears to be a potential regulator to inhibit apoptotic ERS signaling that exerts a protective effect on apoptosis of DCs in the setting of septic challenge.

Immunometabolism determines the fate and function of regulatory T cells. The metabolic phenotype of regulatory T cells (Treg) is affected by various factors. The relationship between Treg metabolism and function of mice with sepsis is not clear. We used liquid chromatography and tandem mass spectrometry (LC-MS/MS) to analyze the metabolic profiles of freshly-isolated spleen Treg cells in mice with sepsis. It was found that in severe infection, activated Treg cells depend on glycolysis and fatty acid oxidation, and inhibition of metabolic pathways has a significant impact on the number and quality of Treg cells. Understanding the metabolic characteristics of Treg cells in the real environment in the body helps to grasp the function of Treg cells and even the overall immune status. Targeting the metabolic pathway of Treg may provide a new method for the treatment of sepsis.

Regulatory T cells (Tregs) play a crucial role in modulating the inflammatory response and participated in sepsis-related immune dysfunctions. However, little is known about the regulatory mechanisms by which Tregs are kept in check during immune responses. Here, we verified the simultaneous expression of interleukin-3 (IL-3) and its receptor (IL-3R) in Tregs. Then, by modulation of IL-3 expression via lentiviral transduction-mediated small interfering RNA, we demonstrated that IL-3 negatively regulated Tregs activity via an autocrine mechanism. Furthermore, we found that anti-IL-3 antibody treatment significantly diminished inflammatory cytokines and organ injury, and improved survival in septic mice, which was associated with enhanced Treg percentage and function. Collectively, these results suggest that IL-3 negatively regulates the activity of Tregs in a previously unrecognized autocrine manner, and plays an important role in the excessive inflammatory response in sepsis, which might be utilized as a therapeutic strategy for the treatment of complications in sepsis.

目的:研究严重烧伤小鼠体内高水平高迁移率族蛋白B1(HMGB1)诱导脾脏树突状细胞(DC)凋亡与内质网应激(ERS)的关系.方法:①复制严重烧伤小鼠模型,检测脾脏与血清中HMGB1的表达.②烧伤模型小鼠和假烫组(37℃水浴)均随机分为3组,分别给予抗HMGB1中和抗体、未免疫兔血清IgG和生理盐水,观察烧伤各组及生理盐水处理假伤组小鼠7 d生存率,并测定各组脾脏DC细胞ERS相关蛋白GRP78和XBP-1的表达.③正常小鼠尾静脉注射10或20μg重组HMGB1,48 h后处死,测定脾脏GRP78和XBP-1的表达.④以1、10、100 ng/ml HMGB1体外刺激健康小鼠的脾脏DC,并进一步应用细胞凋亡抑制剂Salubrinal(Sal)于HMGB1刺激1 h前进行干预,流式细胞术检测DC凋亡;Western blot法检测DC内ERS相关因子GRP78和CHOP的表达水平.分析HMGB1诱导DC细胞凋亡与ERS的内在联系.结果:小鼠烧伤后HMGB1蛋白表达水平增高.抗HMGB1中和抗体对严重烧伤小鼠有明确保护作用,可提高严重烧伤小鼠7 d存活率,显著降低烧伤小鼠脾脏DC内ERS标志分子GRP78以及ERS介导细胞凋亡的关键分子CHOP的蛋白水平.HMGB1(10 ng/ml)刺激可直接诱导DC凋亡以及ERS相关细胞凋亡关键分子CHOP蛋白表达升高;Sal干预可缓解ERS并抑制HMGB1诱导的DC凋亡(P<0.05).结论:HMGB1刺激诱导DC凋亡与ERS相关性细胞凋亡通路激活密切相关,是严重烧伤小鼠脾脏DC功能障碍的重要发病机制.