Rheumatoid arthritis (RA) can be viewed as a disease of barrier failure, in which CX3CR1⁺/TREM2⁺ synovial tissue resident macrophages that form the lining barrier over cartilage and bone become fragmented and disorganized. However, how to therapeutically rebuild this barrier, and how macrophage states transition during repair, remain unclear. We engineered TR-Ab19, a mouse-selective agonistic antibody against TREM2, as a precision tool to initiate and interrogate barrier repair in vivo. TR-Ab19 engages TREM2 linked downstream signaling and redirects synovial macrophages from Clec4d⁺ inflammatory/proliferative programs toward TREM2⁺CX3CR1⁺Aqp1⁺ barrier-like states, thereby rebuilding the lining barrier. Across collagen-induced arthritis (CIA) and serum-transfer arthritis (STA) models, TR-Ab19 reduces synovitis, preserves cartilage and bone microarchitecture, limits osteoclastogenesis, and attenuates systemic cytokines and B cell abnormalities. Single-cell RNA-seq with trajectory and cell cell communication analyses reveal a TREM2 dependent shift toward a barrier-dominant macrophage ecosystem. Together, these findings establish antibody-mediated reprogramming of resident synovial macrophages as a barrier-centered strategy for RA and provide a framework for instructing macrophage niches in chronic inflammation. ### Competing Interest Statement X-D. Sun is an inventor on a patent application covering TR-Ab19 and holds a potential translation interest in its future clinical development; all other authors declare they have no competing interests. National Natural Science Foundation of China, No. 52272278, 92159305, 52402347 National Postdoctoral Program for Innovative Talents, No. BX20230190

Abstract Background This study aimed to elucidate B cell subset pathology in COPD, a poorly characterized area, with a focus on its similarities to and differences from classical autoimmune disorders. Methods The single-cell RNA-sequencing (scRNA-seq) data from COPD and autoimmune diseases were obtained from Gene Expression Omnibus (GEO) for comparative analyses of B cell subsets and functions via differentially expressed genes (DEGs), KEGG, protein-protein interaction (PPI), and cell–cell communication analyses. Serum IgG4 was measured by ELISA and correlated with clinical parameters. The peripheral blood B cells were sorted by flow cytometry for single-cell B cell receptor (BCR) sequencing. A v-Abl/Bcl2 pro-B cell line was stimulated with cigarette smoke extract (CSE) to assess abnormal development in vitro . Results In lung tissue, IgG4 + plasma cells were enriched and expressed BCR activation/inflammatory genes and TNF/NF-κB/MAPK pathways. Serum IgG4 concentrations correlated negatively with pre-and post-bronchodilator FEV 1 /FVC. B cell interacted with monocytes, macrophages, fibroblasts and endothelial cells via IL-1β/IL-6, integrin and chemokine signalling, contributing to chronic inflammation and remodelling. In peripheral blood, transitional T1 B cells were increased, accompanied by λ-chain enrichment and increased IGLV1-47 usage, as well as enrichment of autoimmune pathways. In the bone marrow, the numbers of pre-B I cells were increased while those of small pre-B III cells were reduced, with altered expression of BCR development genes. CSE stimulation of the pro-B cell line reduced λ5 expression in a concentration-dependent manner. Conclusions The autoimmune abnormalities in COPD appear more restricted, although IgG4 antibody generation may contribute to immune-mediated lung damage.

B-1 cells are derived from a subpopulation of B lymphocytes which have a specific developmental process, unique phenotype and location, and distinct functions in comparison with conventional B-2 cells. The origin of B-1 cells is not completely clear, with two existing hypotheses concerning their lineage and differentiation pathways. B-1 cells are located principally in the peritoneal and pleural cavities, but are also distributed in secondary lymphoid tissues, at mucosal sites and in the blood and bone marrow. B-1 cells regulate immune responses and maintain homeostasis by secretion of natural antibodies (nAbs), and participate in the adaptive immune response through phagocytosis and presentation of antigens to T cells. B-1 cells are associated with many diseases including autoimmune, infectious and inflammatory diseases. This review focuses on the origin and biological functions of B-1 cells as well as their involvement in human disease, and discusses advances in the understanding of the heterogeneity of B-1 cells under specific pathophysiological features, as partly clarified by single-cell sequencing analysis.

Objective: In a previous study we have shown that, in the presence of interleukin (IL)-33, repeated, per-nasal challenge of murine airways with Streptococcus pneumoniae (S. pneumoniae) organisms induces human asthma-like airways inflammation. It is not clear, however, whether this effect is unique or manifest in response to other common respiratory pathogens.Methods: To explore this, airways of BALB/c mice were repeatedly challenged per-nasally with formaldehyde-inactivated bacterial bodies in the presence or absence of murine recombinant IL-33. Serum concentrations of S.pneumoniae, Moraxella catarrhalis (M.catarrhalis) and Haemophilus influenzae (H.influenzae) lysates-specific IgE were measured in patients with asthma and control subjects.Results: We showed that in the presence of IL-33, repeated, per-nasal airways exposure to the bodies of these bacteria induced airways hyperresponsiveness (AHR) in the experimental mice. This was accompanied by cellular infiltration into bronchoalveolar lavage fluid (BALF), eosinophilic infiltration and mucous hypertrophy of the lung tissue, with elevated local expression of some type 2 cytokines and elevated, specific IgG and IgE in the serum. The precise characteristics of the inflammation evoked by exposure to each bacterial species were distinguishable.Conclusions: These results suggest that in the certain circumstances, inhaled or commensal bacterial body antigens of both Gram-positive (S. pneumoniae) and Gram-negative (M. catarrhalis and H. influenzae) respiratory tract bacteria may initiate type 2 inflammation typical of asthma in the airways. In addition, we demonstrated that human asthmatic patients manifest elevated serum concentrations of M.catarrhalis- and H.influenzae-specific IgE.

Chronic obstructive pulmonary disease (COPD) is a chronic respiratory condition characterized by persistent inflammation and oxidative stress, which ultimately leads to progressive restriction of airflow. Extensive research findings have cogently suggested that the dysregulation of essential transition metal ions, notably iron, copper, and zinc, stands as a critical nexus in the perpetuation of inflammatory processes and oxidative damage within the lungs of COPD patients. Unraveling the intricate interplay between metal homeostasis, oxidative stress, and inflammatory signaling is of paramount importance in unraveling the intricacies of COPD pathogenesis. This comprehensive review aims to examine the current literature on the sources, regulation, and mechanisms by which metal dyshomeostasis contributes to COPD progression. We specifically focus on iron, copper, and zinc, given their well-characterized roles in orchestrating cytokine production, immune cell function, antioxidant depletion, and matrix remodeling. Despite the limited number of clinical trials investigating metal modulation in COPD, the advent of emerging methodologies tailored to monitor metal fluxes and gauge responses to chelation and supplementation hold great promise in unlocking the potential of metal-based interventions. We conclude that targeted restoration of metal homeostasis represents a promising frontier for ameliorating pathological processes driving COPD progression.

目的 探讨小鼠出生早期气道感染肺炎链球菌(Streptococcus pneumoniae,SP)后,成年期暴露于相同细菌性抗原时对哮喘发生发展的影响及机制研究,为过敏性哮喘防治提供新的研究方向.方法 1 周龄WT BALB/c小鼠滴鼻感染SP,5 周后反复滴鼻灭活SP 菌体及白细胞介素-33(interleukin-33,IL-33)+灭活SP 菌体,检测小鼠气道高反应性(airway hyperresponsiveness,AHR),明确气道/肺部炎性细胞浸润情况及炎症改变;检测血清中免疫球蛋白E(immunoglobulin E,IgE)及SP特异性IgE、IgG浓度和肺组织匀浆中细胞因子表达水平;最后明确肺组织中辅助性T细胞(T helper cell,Th)亚群(Th1、Th2、Th17)和固有淋巴细胞(innate lymphoid cells,ILC)亚群(ILC1、ILC2、ILC3)细胞数变化情况.结果 出生早期SP感染后,成年期单独暴露于相同细菌性抗原未能诱导出哮喘样病理改变;在IL-33 存在下,虽然出生早期SP感染后成年期暴露于相同细菌性抗原依然引起以2 型细胞因子增加为主的混合性炎症,但与未经感染组相比,实验组小鼠的气道高反应性下降;支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF)总细胞计数下降;肺组织中嗜酸性粒细胞浸润减少;黏液分泌明显减少;平滑肌增生减轻;血清中IgE明显下降,然而SP菌体特异性IgE、IgG明显升高;多种细胞因子减少;抑制炎症因子(IL-10)明显升高;虽然ILC2 细胞数量明显升高,但Th1、Th2、Th17 及ILC1细胞数量明显下降.结论 出生早期SP感染可降低成年期小鼠暴露于相同细菌性抗原时诱发的哮喘的严重程度.

Background: Asthma is a common chronic respiratory disease characterized by airways inflammation, hyper -responsiveness and remodeling. IL-37, an anti-inflammatory cytokine, consists of five splice isoforms, that is, a-e. Although it has been previously shown that recombinant human IL-37b is able to inhibit airway inflammation and hyperresponsiveness in animal models of asthma, the effects and difference of other IL-37 isoforms, such as IL-37a on features of asthma are unknown.Methods: Animal models of chronic asthma were established using IL-37a and IL-37b transgenic mice with C57BL/6J background and wild-type (WT) mice sensitized and nasally challenged with ovalbumin (OVA). Airway hyperresponsiveness was measured using FlexiVent apparatus, while histological and immunohisto-logical stainings were employed to measure airways inflammation and remodeling indexes, including goblet cell metaplasia, mucus production, deposition of collagen, hypertrophy of airway smooth muscles and pulmonary angiogenesis.Results: Compared to WT mice, both IL-37a and IL-37b transgenic mice had significant reduced airway hyper -responsiveness and the declined total numbers of inflammatory cells, predominant eosinophils into airways and lung tissues. Furthermore, all features of airways remodeling, including degrees of mucus expression, collagen deposition, hypertrophy of smooth muscles, thickness of airways and neovascularization markedly decreased in IL-37 transgenic mice compared with OVA-treated WT mice.Conclusion: Our data suggest that both IL-37a and IL-37b isoforms are able to not only ameliorate airways inflammation and airways hyperresponsiveness, but also greatly reduce airways structural changes of animal models of chronic asthma.

The disruption and reconstruction of the TREM2(+) tissue resident macrophage (TRM) barrier on the surface of synovial lining play a key role in the activation and "remission" of rheumatoid arthritis (RA), which engender the prediction of this immunologic barrier as a potential driver for the achievement of "cure" in RA. However, strategies to promote the reconstruction of this barrier have not been reported, and the effect of patching this barrier remains unidentified. On the other hand, appropriate piezoelectric stimulation can reprogram macrophages, which has never been exerted on this barrier TRM yet. Herein, we design piezoelectric tetragonal BaTiO3 (BTO) ultrasound-driven nanorobots (USNRs) by the solvothermal synthesis method, which demonstrates satisfactory electromechanical conversion effects, paving the way to generate controllable electrical stimulation under ultrasound to reprogram the barrier TRM by minimally invasive injection into joint cavity. It is demonstrated that the immunologic barrier could be patched by this USNR effectively, thereby eliminating the hyperplasia of vessels and nerves (HVN) and synovitis. Additionally, TREM2 deficiency serum-transfected arthritis (STA) mice models are applied and proved the indispensable role of TREM2 in RA curing mediated by USNR. In all, our work is an interesting and important exploration to expand the classical tetragonal BTO nanoparticles in the treatment of autoimmune diseases, providing a new idea and direction for the biomedical application of piezoelectric ceramics.

目的 分析短期烟草烟雾暴露后肽段激发的慢性阻塞性肺疾病模型小鼠的免疫特点.方法 建立上述短期慢性阻塞性肺疾病模型,行肺组织石蜡切片和支气管肺泡灌洗液分类计数观察气道炎症;有创肺功能检测肺呼吸力学参数;借助 Luminex技术分析细胞因子表达情况;流式细胞术检测小鼠肺组织中辅助T(T helper,Th)细胞和固有淋巴样细胞(innate lymphoid cells,ILCs)亚群的数量及比例变化.结果 短期烟草烟雾暴露后肽段激发可损伤小鼠肺泡;诱导以中性粒细胞浸润为主的气道炎症;3 型细胞因子表达增高;Th17、ILC3 细胞增多,ILC1、ILC2 细胞减少.结论 烟草烟雾暴露后肽段激发诱导的短期慢性阻塞性肺疾病模型以 3 型免疫为主,且ILC3 可能比Th17 的作用更为重要.

为提高医学免疫学教学效果和学生学习兴趣,课题组探索医学免疫学教学新方法,以2020年2月到2021年7月首都医科大学2019级266名临床医学专业学生(包括14名汉语授课留学生)和2018级10名临床医学专业汉语授课留学生作为研究对象.其中,136名学生采用四重教学法,其他140名学生采用传统教学法.教师通过分析学生参与度、阶段性考核和终结性考核成绩,并进行教学满意度调查,来评估线上线下混合式四重教学法在医学免疫学教学中的应用效果.结果显示,在教学过程中,学生课前导读视频的点击率、课堂出勤率、随堂测参与率和作业上交率均在95％以上.学生随堂测的优秀率为39.7％(54/136),课后作业的优秀率为32.4％(44/136).其中,汉语授课留学生的终结性评价成绩[(75.5±8.0)分vs(47.9±18.4)分]和总成绩[(81.6±6.7)分vs(59.3±19.8)分]均高于上一届学生,两者具有统计学意义(P≤0.001,P≤0.01).92.6％(126/136)的学生对基于线上线下混合式四重教学法的整体授课效果表示满意.

Respiratory tract infection early in life plays a significant role in the pathogenesis of asthma. In the present study we examine, using a murine surrogate, the effects of early life respiratory infection with Streptococcus pneumoniae (SP) on adult asthma induced by sensitisation and exposure to house dust mite (HDM) allergen. Mice (one week old) were infected with SP, then 3 weeks later sensitised to HDM emulsified with Al (OH)3 intraperitoneally and challenged intranasally with same allergen for up to a further 5 weeks to establish the asthma surrogate. Outcome measures were quantified using the FlexiVent apparatus, histology and immunohistology, ELISA and flow cytometry. The murine surrogates of asthma infected with SP early in life exhibited significantly more severe disease compared with the controls of mice without SP infection, as shown by airways responsiveness, inflammatory cellular infiltration of the airways, expression of markers of airways remodelling, serum concentrations of HDM-specific IgE and the concentrations of Th2-type cytokines and the numbers of activated Th2 and ILC2 cells in the lung tissues. These data are compatible with the hypothesis that early-life infection of the airways with SP exacerbates, at least in some individuals, subsequent HDM-induced allergic airways inflammation and associated asthma in adulthood in this murine surrogate.

目的 筛选与自身免疫病相关兼职蛋白的B细胞优势表位肽并进行血清学检定.方法 利用DNAMAN软件分析不同物种热休克蛋白70(heat shock protein 70,HSP70)和α-烯醇酶氨基酸序列同源性,IEDB数据库和瓜氨酸化在线平台预测线性B细胞表位和瓜氨酸化修饰位点;间接ELISA检测抗HSP70和α-烯醇酶蛋白瓜氨酸化前后表位肽抗体.结果 同源性分析和IEDB数据库预测得到兼职蛋白HSP70和α-烯醇酶各10个B细胞优势表位肽;瓜氨酸化位点预测显示,其分别有9个和4个位点可能会发生瓜氨酸化修饰,其中5个瓜氨酸化修饰位点与预测表位肽重合.与正常人相比,抗环瓜氨酸肽抗体阳性患者血清抗瓜氨酸化修饰表位肽的抗体滴度明显增高(P＜0.05).结论 采用生物信息学分析和ELISA初步验证的方法有助于筛选自身抗原相关的B细胞优势表位肽.

While environmental aeroallergens and epithelial alarmins such as IL-33 are firmly implicated in asthma, the possible role of Streptococcus pneumoniae (S. pneumoniae) antigens is less clear. To explore this, wild-type BALB/c mice were repeatedly challenged per-nasally with IL-33 and inactivated S. pneumoniae, either agent alone or diluent control. Some animals were rested then later re-challenged with inactivated S. pneumoniae alone. Serum concentrations of S. pneumoniae lysates-specific IgE were measured in patients with asthma and control subjects. Interestingly, in the presence of IL-33, repeated exposure to inactivated S. pneumoniae induced asthma-like pathological changes accompanied by a systemic adaptive immune response. Subsequent re-exposure of the sensitized animals to inactivated S. pneumoniae alone was able to induce such changes. The concentration of S. pneumoniae lysates-specific IgE was significantly elevated in the asthma patients. These data suggest that antigens derived from infectious microorganisms may participate in generating the mucosal inflammation which characterizes asthma.

Allergic disease is one of the most common chronic diseases, which can affect both children and adults,be often caused by allergen-induced unfavorable immune responses, and initiate various symptoms in different organs, including up-/low-airways and skin, such as asthma, atopic dermatitis, and rhinosinusitis. With increasing prevalence of allergic disease worldwide and their impact on the quality of life, new biological therapeutic approaches for these disorders become hot areas of intensive research. Multiple factors are involved and play important role in the pathogenesis of allergic disease, which can promote or trigger T helper 2（Th2）-type immune responses, leading to production of the type 2 cytokines and immunoglobulin E（Ig E）,the two critical events in the allergic diseases. Using monoclonal antibodies to target these molecules, therefore, might provide possible benefits for the patients suffered from these diseases. Apart of those having approved biologics for allergic diseases, some potential targets such as epithelial-derived alarmins thymic stromal lymphopoietin（TSLP） and interleukin 33（IL-33） have been also described and proposed to develop monoclonal antibodies against either these cytokines, their receptors, or both. These new and potential targets have substantially enriched the therapeutic opportunities in the field of allergic diseases. The present review aims to briefly outline the role of monoclonal antibodies targeting the cytokines and immunoglobulin involved in the development of allergic diseases,and to discuss the clinical effects of these antibodies.

Abstract: Urotensin II (UII) is involved in the formation of atherosclerosis, but its role in the stability of atherosclerotic plaques is unknown. The purpose of this study was to observe the dynamic changes in plasma UII and analyze its relationship to the stability of atherosclerotic plaques. One hundred thirty-five consecutive patients with acute coronary syndrome (ACS) were enrolled. The plasma UII levels were measured immediately after admission and during three-month follow-up. A vulnerable plaque model was established using local transfection of a recombinant P53 adenovirus into plaques in rabbits fed with a high-cholesterol diet and subjected to balloon arterial injury. The levels of plasma UII were measured weekly. The changes in plasma UII during the formation of atherosclerotic plaques and before and after plaque transfection were observed. The morphology of the plaques and the expression, distribution, and quantitative expression of UII in the plaques also were observed. Our results showed that the levels of plasma UII in patients with ACS at admission were lower than levels observed at the three-month follow-up. UII dynamic changes and its correlation with plaque stabilities were further verified in rabbits with atherosclerotic vulnerable plaques. The UII levels in rabbits were significantly decreased immediately after the P53 gene transfection, which led to plaque instability and rupture. These results suggested that UII expression was down-regulated in ACS, which may be related to its ability to modulate mechanisms involved in plaque stability and instability.

Asthma is an inflammatory disease of the airways and numerous cytokines contribute to this pathogenesis. It is shown that challenge of airways with IL-33 induces asthma-like pathological changes in mice, but the possible downstream cytokines in this process remain to be characterised. To explore this, we compared changes in the airways of wildtype (WT) and IL-9 deficient mice challenged with IL-33. In line with previous report, per-nasal challenge of WT mice with IL-33 significantly increased the responsiveness of the airways along with infiltration of inflammatory cells, goblet cell hyperplasia, collagen deposition and smooth muscle hypertrophy, and the expression of cytokines compared with control group. Surprisingly, all of these pathological changes were significantly attenuated in IL-9 deficient mice following identical IL-33 challenge. These data suggest that IL-9 is one downstream cytokine relevant to the effects of IL-33 in asthmatic airways and consequently a potential therapeutic target for the treatment of asthma.

类风湿性关节炎(RA)的典型病理改变是滑膜炎和骨破坏,最终导致关节畸形而致残.Wnt信号通路在滑膜炎和骨破坏中发挥广泛的作用,是RA病情进展的重要因素.Wnt信号通路参与RA软骨细胞、成骨细胞和破骨细胞等的功能障碍有密切关系,并且促进RA相关病理因子的产生.本文就Wnt信号通路与RA炎症和骨侵蚀的关系及靶向该通路治疗的相关研究进行综述.

Wnt5a signalling plays pathological roles in synovial inflammation and bone destruction. In the present study, we designed four human Wnt5a-based DNA recombinants and detected their effects on immunogenicity and anti-rheumatism in a collagen-induced arthritis (CIA) model. Histomorphometry and micro-CT scanning showed that the phWnt5a-NL was superior to other recombinants because it resulted in decreased severity of arthritis, histopathological scores of synovial inflammation and bone erosion in CIA mice. In addition, ELISA and TRAP staining showed that the phWnt5a-NL-immunized CIA mice had reductions in the serum concentrations of the rheumatoid-associated cytokines IL-1β and RANKL and in osteoclastogenesis. Furthermore, flow cytometry showed that the phWnt5a-NL treatment increased the percentage of Treg cells. Finally, western blotting analysis showed that the phWnt5a-NL-immunization interrupted β-catenin and JNK expression in osteoclast precursors derived from the CIA mice. The results suggest that depleting the carboxy-terminus in hWnt5a-based DNA recombinants may be beneficial for the treatment of chronic inflammatory disorders involving bone resorption.

Objective: Histone deacetylases (HDACs) play an important role in dysregulation of histone acetylation/deacetylation, which is the main driving force of the progression of pulmonary fibrosis. Here we investigated the changes in histone acetylation/deacetylation, and the contribution of specific class I and class II HDACs in the progression of pulmonary fibrosis. Methods: Male C57BL/6J mice received a single dose of tracheal administration of bleomycin to establish the pulmonary fibrosis model. The changes in acetylation rate of histone 3 (H3) and histone 4 (H4), and the activity of HDAC2 and HDAC4 in the lung tissue during the progression from alveolitis to pulmonary fibrosis were measured. Results: The acetylation rate of H3/H4 significantly decreased during alveolitis and the early and middle stages of fibrosis, but restored in the late stage of fibrosis. Correlation analysis showed that H4 deacetylation affected both alveolitis and pulmonary fibrosis. H3 deacetylation only affected alveolitis. HDAC2 activity significantly increased in the middle and late stages of pulmonary fibrosis. There was no significant difference in HDAC4 activity between bleomycin and saline groups. However, HDAC4 activity changed significantly with the progression of the disease in bleomycin group. The changes in HDAC2 and HDAC4 activity were different. HDAC2 had long-lasting effects, while HDAC4 had transient effects. Correlation analysis showed that HDAC2 and HDAC4 activity was positively correlated with alveolitis score and fibrosis score. Conclusions: The changes in histone acetylation may directly regulate the gene expression of inflammatory cytokines/fibronectin and thus affect the progression of pulmonary fibrosis. The injury-induced histone deacetylation switched into acetylation at the late stage of pulmonary fibrosis, which may be involved in the repair process. HDAC2 is mainly involved in the chronic progression of pulmonary fibrosis, and HDAC4 is mainly involved in early stress response to pulmonary fibrosis.

目的 制备同时拮抗肿瘤坏死因子α(tumor necrosis factor α,TNF-α)和核因子κB受体活化因子配体(receptor activator of NF-κB ligand,RANKL)的人源化单克隆抗体(h8G12),通过单关节炎小鼠模型,评估h8G12在抑制TNF-α引起的炎症反应和拮抗RANKL引起的骨破坏中的保护作用.方法 培养稳定表达h8G12的CHO细胞株,观察细胞生长状态,用间接ELISA检测细胞培养上清中h8G12的表达水平.纯化的h8G12经SDS-PAGE、Western blot分析及鉴定,用间接ELISA观察其亲和力.通过向DBA/1小鼠膝关节腔注射人TNF-α重组蛋白和人RANKL重组蛋白,建立单关节炎小鼠模型.用组织学评估观察不同给药方案[阴性对照组、阳性对照组、阿达木单抗(adalimumab,ADA)组和h8G12组]对小鼠单关节炎引起的炎症浸润、软骨侵蚀、膝关节腔内破骨细胞分化的保护作用.结果 CHO细胞株培养96 h时细胞生长状态良好,可稳定分泌h8G12;纯化的h8G12纯度可达90％,Western blot可见特异性条带,且可与rhTNF-α和rhRANKL结合.在单关节炎小鼠模型中,苏木精-伊红染色显示,h8G12组关节腔、周围软组织及骨髓腔内炎性细胞浸润明显少于阳性对照组,炎症评分降低了50％,治疗效果与ADA相似.甲苯胺蓝染色显示,h8G12组病理评分出现显著下降,h8G12治疗后小鼠关节结构相对完好,关节软骨厚度接近正常水平.抗酒石酸酸性磷酸酶染色显示,h8G12组关节腔内破骨细胞明显减少.结论 h8G12可有效抑制TNF-α引起的炎症反应和拮抗RANKL引起的骨破坏,为类风湿关节炎的治疗提供了新方法.