Molecular immunology最新文献

{"title":"Photobiomodulation regulates inflammation and autophagy in spinal cord injury through NLRP3/Caspase-1/IL-1β pathway by targeting TLR2","authors":"Xiaoshuang Zuo ,&nbsp;Cheng Ju ,&nbsp;Zhihao Zhang ,&nbsp;Xinghui Wei ,&nbsp;Yangguang Ma ,&nbsp;Zhiwen Song ,&nbsp;Jiawei Zhang ,&nbsp;Liang Luo ,&nbsp;Zhijie Zhu ,&nbsp;Zhe Wang ,&nbsp;Xueyu Hu","doi":"10.1016/j.molimm.2025.03.014","DOIUrl":"10.1016/j.molimm.2025.03.014","url":null,"abstract":"<div><div>After spinal cord injury (SCI), peripherally derived macrophages infiltrated the injury area to exert inflammatory effects, causing barriers to the repair of spinal cord injury. Our previous study confirmed that photobiomodulation (PBM) could promote the motor function recovery and inhibit the secretion of inflammatory cytokines after SCI, moreover, PBM also has a role in promoting autophagy, but the mechanism is not clear. Therefore, we aimed to investigate whether PBM promotes autophagy by regulating the inflammatory response of macrophages, which in turn regulates functional repair after SCI. Male C57/BL6 mice were used to prepare a model of clamped spinal cord injury, and PBM irradiation was performed for 28 consecutive days, which showed that motor function of the mice was improved. We observed that autophagy proteins (LC3, Beclin-1 and P62) were inhibited and inflammasome-related proteins (NLRP3, Caspase-1 and IL-1β) expression was significantly enhanced in SCI mice. We analyzed the RNA sequencing (RNA-seq) of SCI, SCI+PBM treated mice in combination with autophagy database. The results showed 25 differentially expressed genes (DEGs). Protein-protein interaction (PPI) network and Hub gene analysis revealed TLR2 as a key molecule in the regulation of autophagy levels by PBM after SCI. We performed preliminary analysis in macrophages cultured in <em>vitro</em> and observed that PBM suppressed the expression of TLR2 and inflammasome-related proteins in M1-type macrophages and promoted the expression of autophagy proteins. Subsequently, we used an agonist of TLR2 (CU-T12–9) to up regulate TLR2 expression and observed that macrophage autophagy was inhibited and inflammatory response was enhanced. After PBM irradiation, the effect of CU-T12–9 was counteracted. Taken together, PBM promotes autophagy and attenuates the inflammatory response by regulating TLR2, a key molecule of autophagy in spinal cord injury.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"182 ","pages":"Pages 1-10"},"PeriodicalIF":3.2,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143724034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brucella lipopolysaccharide deficiency with lipid A induces robust T cells immune response","authors":"Jian-Dong Zhang,&nbsp;Qun Wang,&nbsp;Hong-Xia Hu,&nbsp;Kai-Xuan Guo,&nbsp;Chao-Yue Guo,&nbsp;Huan-Chun Chen,&nbsp;Zheng-Fei Liu","doi":"10.1016/j.molimm.2025.03.006","DOIUrl":"10.1016/j.molimm.2025.03.006","url":null,"abstract":"<div><div><em>Brucella</em>, an opportunistic intracellular parasitic bacterium, is classified as a Gram-negative organism. Lipopolysaccharide (LPS), as primary virulence factor of <em>Brucella</em>, includes lipid A, O-antigen, and core polysaccharide, with lipid A being the principal component. The atypical structure of <em>Brucella</em> LPS, noted for its very-long-chain fatty acids, may suppress the host immune response, thus facilitating chronic disease development. The mechanism by which these chains induce immunosuppression remains poorly understood.This study aimed to investigate these chains through deletion of the <em>BacA</em> gene. We extracted LPS to stimulate Bone Marrow-Derived Dendritic Cells (BMDCs) <em>in vitro</em> and co-cultured them with T cells to induce proliferation and differentiation. The <em>in vivo</em> immune response to LPS was evaluated through routine blood tests, CD4 and CD8 assays, and lymphocyte stimulation indices. Our findings demonstrate that wild-type LPS from <em>B. melitensis</em> (Bm-WT) does not elicit an immunostimulatory response <em>in vitro</em>; rather, it promotes immune suppression <em>in vivo</em>. In contrast, LPS derived from <em>B. melitensis</em> with a mutated <em>BacA</em> gene (Bm-Δ<em>BacA</em>) disrupts the immune suppression and encourages the production of inflammatory factors. These findings underscore the crucial role of modifying lipid A through molecular biology techniques to advance bacterial vaccines and adjuvants.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"182 ","pages":"Pages 11-19"},"PeriodicalIF":3.2,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143724142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypericin impedes M2 macrophage polarization and protects against Hepatocellular carcinoma","authors":"Xinru Wen ,&nbsp;Xianling Wang ,&nbsp;Qing Yao ,&nbsp;Simin Chen ,&nbsp;Chengwei Li ,&nbsp;Congyang Zheng ,&nbsp;Ang Huang ,&nbsp;Xiaoyan Zhan ,&nbsp;Zhaofang Bai ,&nbsp;Xiaohe Xiao","doi":"10.1016/j.molimm.2025.03.012","DOIUrl":"10.1016/j.molimm.2025.03.012","url":null,"abstract":"<div><h3>Background</h3><div>There has been increasing evidence that M2 polarization, which is essential for tumor growth, is present in most tumor-associated macrophages. Hypericin is the major component of the Traditional Chinese Medicine <em>Hypericum perforatum</em>. Hypericin exhibits antitumor activities, but its regulation on M2 macrophage polarization and the protective against Hepatocellular carcinoma (HCC) remains unknown.</div></div><div><h3>Methods</h3><div>IL-4 was used to induce bone marrow-derived macrophages (BMDMs) to differentiate into M2 macrophages, the effect of hypericin on M2 polarization of BMDMs was investigated, mRNA level of M2-related genes was determined using RT-qPCR and flow cytometry. Furthermore, the effect of culture medium of M2 macrophage (M2-CM) pretreated with hypericin or not on the proliferation, migration, and invasion of Hepa1–6 cells was studied. To investigate the mechanism, the PI3K/AKT signaling pathway, which is critical in macrophage polarization was tested. A mouse model of HCC was established by subcutaneous implantation of H22 cells, the impact of Hyp on tumor growth and M2 macrophage polarization in tumor tissues was identified.</div></div><div><h3>Results</h3><div>In the present study, we found that Hyp significantly inhibited M2 polarization of macrophages, as indicated by decreased expression of CD206 and M2-related markers, moreover, Hyp suppressed the M2-CM-induced proliferation, invasion and migration of Hepa1–6 cells. Hyp manifested an inhibitory effect on the PI3K/AKT signaling pathway during the differentiation of M2 macrophages. In vivo experiments showed that Hyp greatly suppressed tumor growth and reduced M2 macrophage polarization in tumor tissues.</div></div><div><h3>Conclusion</h3><div>Hyp impedes the growth, proliferation, invasion and migration of HCC by inhibiting M2 macrophages polarization via the PI3K/AKT signaling pathway, our data demonstrate that hypericin may be a promising candidate for HCC treatment.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"181 ","pages":"Pages 160-168"},"PeriodicalIF":3.2,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143705612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuritin-specific antibody impedes the Treg-mediated suppression of anti-tumor immunity and enhances response to anti-PD1","authors":"Kaimin Zhang ,&nbsp;Taowen Zhao ,&nbsp;Fraooq Riaz ,&nbsp;Yikui Li ,&nbsp;Ping Wei ,&nbsp;Xiang Fang ,&nbsp;Zhiyi Zhou ,&nbsp;Wei Kou ,&nbsp;Fan Pan","doi":"10.1016/j.molimm.2025.03.013","DOIUrl":"10.1016/j.molimm.2025.03.013","url":null,"abstract":"<div><div>Regulatory T cells (Tregs) and effector T cells play critical roles in tumor immunity, with Tregs suppressing immune responses and contributing to an immunosuppressive tumor microenvironment (TME). Neuritin-1 (Nrn), a neuropeptide, has been identified to enhance Treg expansion. However, its role in T cell biology and tumor development remains unclear. We demonstrated that Nrn is highly expressed in the in-vitro-induced Tregs (iTregs). Functionally, Nrn promoted iTreg differentiation in a dose-dependent manner, while Nrn deletion or anti-Nrn antibody treatment significantly inhibited iTreg differentiation. Additionally, Nrn suppressed IL-2 transcription and secretion in T cells, impairing T cell activation and pro-inflammatory cytokine production. Treg-specific Nrn knockout mice exhibited reduced B16 melanoma tumor growth, decreased Treg infiltration, and increased effector T cell infiltration. Conversely, overexpression of Nrn accelerated B16 melanoma tumor progression by enhancing Treg-mediated suppression. Importantly, we developed the first anti-Nrn antibody, which effectively reduced tumour growth, decreased Treg infiltration, and enhanced effector T-cell activity. Importantly, anti-Nrn synergistically worked with anti-PD1 and improved the anti-PD1 response by reducing Tregs and increasing effector function in tumor-infiltrated T cells, resulting in enhanced tumor regression. Our findings identify Nrn as a critical regulator of Treg differentiation and effector T cell suppression, contributing to tumor progression. Targeting Nrn alone or combined with anti-PD1 therapy represents a promising strategy to enhance anti-tumor immunity.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"181 ","pages":"Pages 148-159"},"PeriodicalIF":3.2,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143705611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Compound C1 reduced inflammation and activated autophagy in alveolar macrophages in mice","authors":"Qi Sheng ,&nbsp;Jie Zhao ,&nbsp;Shujun Chen ,&nbsp;Jingmin Zeng ,&nbsp;Shaogui Wang ,&nbsp;Jinping Wang","doi":"10.1016/j.molimm.2025.03.010","DOIUrl":"10.1016/j.molimm.2025.03.010","url":null,"abstract":"<div><div>The purpose of this study was to investigate the therapeutic effect of Compound C1 (Comp-C1) on lipopolysaccharide (LPS) -mediated sepsis acute lung injury (SALI) in vitro alveolar macrophage model and its regulatory mechanism. In vitro cultured mouse alveolar macrophages (MH-S) were treated with LPS. The expression and localization of transcription factor EB (TFEB) after LPS stimulation were detected. Then the cells were treated with LPS (1 μg/mL) and Comp-C1 (1 μM) for 24 h. RT-qPCR and Western Blot were used to detect the mRNA expression of inflammatory factors. Western blot was used to detect the expression of TFEB, lysosome-associated membrane protein 1 (LAMP1), P62 and microtubule-associated protein 1 light chain 3B (LC3B). TFEB-EGFP-Hela and mCherry-EGFP-LC3-Hela cells were used to detect the changes of TFEB nuclear expression and intracellular autophagic flux after Comp-C1 administration by immunofluorescence. The results showed that the expression of inflammatory factors was the highest after 1 μg / mL LPS stimulation for 24 hours. At the same time, the expression of TFEB gene and protein decreased after LPS stimulation, and the content of TFEB in cytoplasm and nucleus decreased by separating cytoplasmic and nuclear proteins. The content of LAMP1 decreased, and the expression of autophagy-related proteins reflected the inhibition of autophagy. After treatment with Comp-C1, the inflammatory factors were significantly decreased, the expression of TFEB and LAMP1 was significantly increased, and the expression of autophagy genes in the cells was restored. The up-regulation of TFEB nuclear expression after Comp-C1 administration was determined by TFEB-EGFP-Hela cells, and the recovery of autophagy flux and alveolar macrophage function after Comp-C1 administration was determined by mCherry-EGFP-LC3-Hela cells. Therefore, Comp-C1 can alleviate LPS-induced MH-S autophagy dysfunction and reduce inflammatory response by up-regulating TFEB in mouse alveolar macrophages, suggesting that Comp-C1 can be used as a potential drug for the treatment of SALI</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"181 ","pages":"Pages 139-147"},"PeriodicalIF":3.2,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143697123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Darutoside promotes skin wound healing via regulating macrophage polarization","authors":"Linpei Gao ,&nbsp;Jing Su ,&nbsp;Lijia Guo ,&nbsp;Sheng Lin ,&nbsp;Junji Xu ,&nbsp;Yi Liu","doi":"10.1016/j.molimm.2025.03.008","DOIUrl":"10.1016/j.molimm.2025.03.008","url":null,"abstract":"<div><div>Wound healing is a complex and dynamic process of tissue formation, while polarization of macrophages plays an important role during this process. Darutoside is one of the major components of the ethanol extract from Siegesbeckia, which has the effects of anti-inflammation, healing rheumatism and promoting joint health. To investigate whether darutoside could promote wound healing, we established full-thickness excisional cutaneous wound healing model in C57/BL6 mice and applied darutoside on the skin wounds. The results showed that darutoside can improve wound healing in mice. Mechanistically, we treated RAW264.7 and macrophages with darutoside <em>in vitro</em>, and found that darutoside inhibited the LPS-induced polarization and pro-inflammatory cytokines expression in macrophages by inhibiting NF-κB signaling pathway. For <em>in vivo</em> study, we also found that darutoside could promote the growth of epithelial cells in wound tissue and inhibit the expression of iNOS+ macrophages around wound tissue by IHC staining. In addition, we also found that darutoside could inhibit the expression of inflammatory factors in wound tissue by PCR. Our data revealed that darutoside could promote wound healing by regulating macrophage polarization via inhibition of NF-κB signaling pathway.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"181 ","pages":"Pages 129-138"},"PeriodicalIF":3.2,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143697112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in dendritic cell-based therapeutic tumor vaccines","authors":"Simin Qin ,&nbsp;Jintong Na ,&nbsp;Qun Yang ,&nbsp;Jing Tang ,&nbsp;Yamin Deng ,&nbsp;Liping Zhong","doi":"10.1016/j.molimm.2025.03.005","DOIUrl":"10.1016/j.molimm.2025.03.005","url":null,"abstract":"<div><div>Dendritic cell-based therapeutic tumor vaccines are an active immunotherapy that has been commonly tried in the clinic,traditional treatment modalities for malignant tumors, such as surgery, radiotherapy and chemotherapy, have the disadvantages of high recurrence rates and side effects. The dendritic cell vaccination destroys cells from tumors by means of the patient's own system of immunity, a very promising treatment. However, due to the suppression of the tumor immune microenvironment, the difficulty of screening for optimal specific antigens, and the high technical difficulty of vaccine production. Most tumor vaccines currently available in the clinic have failed to produce significant clinical therapeutic effects. In this review, the fundamentals of therapeutic dendritic cells vaccine therapy are briefly outlined, with a focus on the progress of therapeutic Dendritic cells vaccine research in the clinic and the initiatives undertaken to enhance dendritic cell vaccinations' anti-tumor effectiveness. It is believed that through the continuous exploration of novel therapeutic strategies, therapeutic dendritic cells vaccines can play a greater role in improving tumor treatment for tumor patients.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"181 ","pages":"Pages 113-128"},"PeriodicalIF":3.2,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143684739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IL-33 facilitates endoplasmic reticulum stress and pyroptosis in LPS-stimulated ARDS model in vitro","authors":"Pei-long Li ,&nbsp;Hong-min Fu ,&nbsp;Kai Liu ,&nbsp;Hai-feng Liu ,&nbsp;Ming-ze Sui ,&nbsp;Jia-wu Yang","doi":"10.1016/j.molimm.2025.03.007","DOIUrl":"10.1016/j.molimm.2025.03.007","url":null,"abstract":"<div><h3>Background</h3><div>Inflammatory activation of pulmonary microvascular endothelial cells (PMVECs) initiated by endoplasmic reticulum stress (ERS) contributes to acute respiratory distress syndrome (ARDS). Interleukin 33 (IL-33) has pro-inflammatory and transcriptional regulatory effects. Therefore, this study intends to investigate the effect of IL-33 on ERS and pyroptosis in the hPMVEC.</div></div><div><h3>Methods</h3><div>The hPMVEC-associated ARDS cell model was induced with lipopolysaccharide (LPS) and treated with 4-PBA (ERS inhibitor), thapsigargin (ERS activator), or IL-33 neutralizing antibody. Western blot and IF staining were performed to analyze the expression of cell-cell junction-associated (Cx37, Cx40, Cx43, Occludin, and Zo-1), ERS-associated (ATF6, IRE1a, and p-Erk), and pyroptosis-associated (NLRP3, IL-1β, and IL-18) proteins. Bioinformatics identified differential expression of IL-33 in ARDS-related datasets and targets of thapsigargin.</div></div><div><h3>Results</h3><div>IL-33 was highly expressed in serum of ARDS patients and in ARDS cohorts from multiple GEO datasets (GSE237260, GSE216635, GSE89953, GSE263867, and GSE5883), and was significantly correlated with clinical features. 4-PBA decreased permeability and IL-33 levels, and increased Cx37, Cx40 and Cx43 levels in the ARDS cell model. IL-33 neutralizing antibody effectively augmented the levels of Cx43 and Zo-1, and diminished the levels of ATF6, IRE1a, p-Erk, NLRP3, IL-1β, IL-18, ROS, and Ca^2 +. The therapeutic effect of IL-33 neutralizing antibodies was reverted by thapsigargin. Moreover, the Swiss Target Prediction and Super-PRED databases obtained 140 and 122 thapsigargin targets, which had 14 intersections. These intersections were associated with immunity, inflammation, apoptosis, pyroptosis, and Ca²⁺ homeostasis. Notably, CASP8 and PTGS2 interacted with IL-33 in these intersections.</div></div><div><h3>Conclusion</h3><div>IL-33 promotes ERS and pyroptosis, thereby contributing to barrier damage in ARDS cell models. IL-33 is a promising therapeutic target for ARDS.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"181 ","pages":"Pages 102-112"},"PeriodicalIF":3.2,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of the anti-inflammatory, anti-oxidant and anti-apoptotic activity of 18β- glycyrrhetinic-acid on the model of LPS-induced lung injury in rats","authors":"Selina Aksak Karamese ,&nbsp;Volkan Gelen ,&nbsp;Gulfem Nur Yildiz ,&nbsp;Kevser Albayrak ,&nbsp;Semin Gedikli ,&nbsp;Adem Kara ,&nbsp;Murat Karamese","doi":"10.1016/j.molimm.2025.03.009","DOIUrl":"10.1016/j.molimm.2025.03.009","url":null,"abstract":"<div><h3>Introduction</h3><div>Our aim was to investigate the protective effects of 18β-Glycyrrhetinic-acid (50 and 100 mg/kg i.g) on LPS-induced rat sepsis model by analyzing some immune mechanisms including inflammation, apoptosis, and oxidative stress parameters by different techniques such as Mallory’s Trichome staining, ELISA, tissue biochemistry and Western Blotting.</div></div><div><h3>Methods</h3><div>Forty-eight Sprague Dawley rats divided into 6 groups as follows: (i) Control, (ii) DMSO, (iii) LPS induced-Sepsis, (iv) LPS induced-Sepsis+ 18β-GA 50 mg/kg, (v) LPS induced-Sepsis + 18β-GA 100 mg/kg, (vi) 18β-GA 100 mg/kg. The pro-inflammatory cytokine (IFNγ, IL-1ß, TNF- α) levels were measured by ELISA technique. All rat’s lung tissues micrographed with Mallory’s Trichome stain. Oxidative stress parameters (MDA, GSH, SOD, NRF2, and HO-1), TLR4 signaling, and apoptotic proteins (Bcl-2 and Caspase-3) were detected by using tissue biochemistry and Western blotting.</div></div><div><h3>Results</h3><div>LPS administration caused a significant increase in all pro-inflammatory cytokine and oxidant levels. Shedding of bronchiolar epithelium, thickening of alveolar septa and vascular dilatation in LPS groups’ lung tissue were revealed according to the histopathological findings. The H-scores of 18β-GA50 +LPS and 18β-GA100 +LPS groups were significantly lower than LPS groups’ (p &lt; 0.05). When lung tissue protein expression profiles were analyzed for HO-1, TLR4, IL-1β, TNF-α, Bcl-2, and Caspase-3 expression was higher in the LPS group than in the control. In addition, NRF2 and Bcl-2 protein expressions were higher in control, DMSO and 18β-GA100 groups, while it was the lowest level in LPS group.</div></div><div><h3>Conclusion</h3><div>18β-GA demonstrates significant protective effects against LPS-induced lung injury in rats by modulating various immune mechanisms. These findings indicate that 18β-GA, particularly at the higher dose, may be a potential therapeutic agent in managing sepsis by mitigating inflammation, oxidative stress, and apoptosis in lung tissue. The inflammation and oxidative stress parameters were decreased and the apoptotic markers were increased in treatment group. Further molecular studies should be performed to investigate the roles of some significant cellular signaling pathways.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"181 ","pages":"Pages 93-101"},"PeriodicalIF":3.2,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dock2 deficiency reveals abnormal activation and differentiation of T cells under the physiological condition","authors":"Li Xu ,&nbsp;Weijie Shen ,&nbsp;Jun Chen ,&nbsp;Huiru Lv ,&nbsp;Wenji He ,&nbsp;Tian-Sheng He ,&nbsp;Tianfu Guo ,&nbsp;Zhiping Liu","doi":"10.1016/j.molimm.2025.03.004","DOIUrl":"10.1016/j.molimm.2025.03.004","url":null,"abstract":"<div><div>Previous research has demonstrated that <em>Dock2</em> deficiency results in a reduction in both the quantity and proliferation rate of T cells, thereby heightening the host's vulnerability to various infections. Nevertheless, the impact of DOCK2 on T cell activation remains unexplored. In this study, we employed flow cytometry to assess the activation phenotype of T cells in the peripheral lymphoid tissues of wild-type (<em>Dock2</em>^<em>+/+</em>), DOCK2 heterozygous (<em>Dock2</em>^<em>+/-</em>) and DOCK2 knockout (<em>Dock2</em>^<em>-/-</em>) mice. Our findings revealed that, in comparison to <em>Dock2</em>^<em>+/+</em> mice, <em>Dock2</em>^<em>-/-</em> mice exhibited increased expression levels of CD44 and CD69 on CD4⁺ and/or CD8⁺ T cells within spleen and mesenteric lymph nodes (MLN). Additionally, there was a significant elevation in the proportions of IFN-γ⁺/CD4⁺, IFN-γ⁺/CD8⁺ and IL-4⁺/CD8⁺ T cells. Furthermore, the percentage of IL-17a⁺/CD4⁺ and IL-17a⁺/CD8⁺ T cells in the MLN of <em>Dock2</em>^<em>-/-</em> mice was higher than that observed in <em>Dock2</em>^<em>+/+</em> mice. These results suggest that <em>Dock2</em> deficiency induces aberrant T cell activation in peripheral lymphoid tissues. To further investigate the underlying mechanisms of this phenomenon, we conducted transcriptome sequencing on CD8⁺ T cells collected from all groups of mice. The results indicate that <em>Ccr2</em> and <em>Ifng</em> are potentially pivotal genes involved in the aberrant activation of T cells in <em>Dock2</em>^<em>-/-</em> mice. These findings contribute to elucidating the host defense mechanisms against foreign pathogens and advance our comprehension of the role of cytoskeleton-related proteins in the regulation of cellular immunity.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"181 ","pages":"Pages 75-83"},"PeriodicalIF":3.2,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143641859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}