Molecular immunology最新文献

{"title":"CD305 participates in abnormal activation of memory CD4+ T cells in patients with RA and attenuates collagen-induced arthritis","authors":"Minghua Lyu ,&nbsp;Pengtao Jiang ,&nbsp;Bin Li ,&nbsp;Zhifang Hu ,&nbsp;Na Guo","doi":"10.1016/j.molimm.2024.07.010","DOIUrl":"10.1016/j.molimm.2024.07.010","url":null,"abstract":"<div><p>Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that mainly affects the joints. Studies have shown that memory CD4⁺ T cells play an important role in the pathogenesis of RA. This study investigated the expression and function of CD305 on human memory CD4⁺ T cells and the effects of CD305 activating antibody on collagen-induced arthritis. The results showed that CD305 expression was significantly decreased on circulating memory CD4⁺ T cells from patients with RA and its mean fluorescence intensity (MFI) was negatively correlated with DAS28. Moreover, CD305 inhibited the activation of memory CD4⁺ T cells by down-regulating CD69 and CD25 and the production of IFN-γ, IL-4, and IL-17A induced by anti-CD3/CD28 antibodies. In addition, activation of CD305 inhibited the severity of disease in collagen-induced arthritis. In summary, CD305 reduction may mediate the excessive activation of memory CD4⁺ T cells and participate in the development of RA. It can be used as a predictive marker of disease activity and has potential medicinal value in the treatment of RA.</p></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"173 ","pages":"Pages 80-87"},"PeriodicalIF":3.2,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141855985","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":"Inhibition of DNMT1 attenuates experimental food allergy","authors":"Linjing Li ,&nbsp;Wenjing Pang ,&nbsp;Lingzhi Xu ,&nbsp;Yuanyi Zhang ,&nbsp;Hanqing Zhang ,&nbsp;Liming Zhu ,&nbsp;Yuyi Li ,&nbsp;Huapeng Lin ,&nbsp;Lihua Mo ,&nbsp;Yu Liu ,&nbsp;Lei Wang ,&nbsp;Pingchang Yang","doi":"10.1016/j.molimm.2024.07.009","DOIUrl":"10.1016/j.molimm.2024.07.009","url":null,"abstract":"<div><h3>Background</h3><p>The treatment of food allergy (FA) needs improvement. The treatment of immune disorders can be improved by regulating epigenetic marks, which is a promising method. The objective of this research is to alleviate experimental FA by employing an inhibitor of DNA methyltransferase-1 (DNMT1).</p></div><div><h3>Methods</h3><p>Ovalbumin was used as the specific antigen to establish a mouse model of FA. Intestinal IL-35⁺ regulatory B cells (Breg cells) were isolated from FA mice, and characterized using immunological approaches.</p></div><div><h3>Results</h3><p>FA mice had a lower frequency of IL-35⁺ Breg cells, which was inversely correlated with their FA response. The quantity of IL-35 was lower in intestinal Breg cells from FA mice. Hypermethylation status was detected in the <em>Il35</em> promoter, which was accompanied with high levels of H3K9me3. Enforced expression of DNMT1 hindered the promoter activity of the <em>IL35</em> gene. Administration of an inhibitor of DNMT1 (RG108) restored the immune regulatory capacity of FA intestinal Bregs, and effectively suppressed the expression of DNMT1, and attenuated experimental FA.</p></div><div><h3>Conclusions</h3><p>The elevated quantity of DNMT1 in intestinal Breg cells compromises the expression of IL-35 and affects the immune regulatory functions, which facilitates the development of FA. The immune regulatory functions of intestinal Breg cells are restored and experimental FA is attenuated by inhibiting DNMT1.</p></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"173 ","pages":"Pages 71-79"},"PeriodicalIF":3.2,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141788705","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":"Single-cell transcriptome sequencing partially revealed the changes of T cells in the early stage of aging kidney","authors":"Xinyi Yu ,&nbsp;Shuying Li ,&nbsp;Jinjie Zhong ,&nbsp;Xiaoqian Ji ,&nbsp;Huizhong Xu ,&nbsp;Qilin Chen ,&nbsp;Qiu Li","doi":"10.1016/j.molimm.2024.06.005","DOIUrl":"10.1016/j.molimm.2024.06.005","url":null,"abstract":"<div><p>Aging is a gradual, inevitable physiologic process. The organ aging is related to the persistence of chronic inflammation, but the understanding of inflammatory state during renal aging is lacking currently. Single-cell transcriptome sequencing was performed on aging mouse kidney to reveal the molecular phenotype and composition changes of different cell types. In the early stage of aging, immune cells such as T, B cells and mononuclear macrophages increased in kidney. The molecular state of T cells in aging kidney changed and polarized. Among them, we identified a group of <em>GZMK</em>⁺ CD8 ⁺ T cells with high expression of <em>Eomes</em>, <em>Pdcd1</em> and <em>Ifng</em> and a group of <em>Il17a</em>⁺ T cells with high expression of <em>Il17a</em> and <em>Il23r</em>. Moreover, the cytokines and inflammations can aggravate tissue damage eventually. Furthermore, we found the interaction between different types of epithelial cells and T cells increased during the renal aging. These results identify the changes of T cells in the early stage of aging kidney and suggest that GZMK⁺CD8⁺ T cells might be a potential target to ameliorate age-associated dysfunctions of kidney(Graphical Abstract).</p></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"173 ","pages":"Pages 61-70"},"PeriodicalIF":3.2,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0161589024001159/pdfft?md5=e40f3ae9a5f074ef73bb2a3f3132edf6&pid=1-s2.0-S0161589024001159-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141766745","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":"Evaluation of the prophylactic effect of egg yolk antibody (IgY) produced against the recombinant protein containing IpaD, IpaB, StxB, and VirG proteins from Shigella","authors":"Alireza Felegary ,&nbsp;Shahram Nazarian ,&nbsp;Mojtaba Zafarmand-Samarin ,&nbsp;Davoud Sadeghi ,&nbsp;Javad Fathi ,&nbsp;Hossein Samiei-Abianeh","doi":"10.1016/j.molimm.2024.07.002","DOIUrl":"10.1016/j.molimm.2024.07.002","url":null,"abstract":"<div><h3>Introduction</h3><p>Shigellosis is a gastrointestinal disease causes high morbidity and mortality worldwide, however, there is no anti-<em>Shigella</em> vaccine. The use of antibiotics in shigellosis treatment exacerbates antibiotic resistance. Antibodies, particularly egg yolk antibody (IgY), offer a promising approach to address this challenge. This study aimed to investigate the prophylactic effect of IgY produced against a recombinant chimeric protein containing the immunogens IpaD, IpaB, StxB, and VirG from <em>Shigella</em>.</p></div><div><h3>Methods</h3><p>The chimeric protein, comprising IpaD, IpaB, StxB, and VirG, was expressed in <em>E. coli</em> BL21 and purified using the Ni-NTA column. Following immunization of chickens, IgY was extracted from egg yolk using the PEG-6000 method and analyzed through SDS-PAGE and ELISA techniques. Subsequently, the prophylactic efficacy of IgY was assessed by challenging of mice with 10 LD50 of <em>S. dysenteriae</em> and administering different concentrations of IgY (1.25, 2.5, 5, and 10 mg/kg) under various time conditions.</p></div><div><h3>Results</h3><p>The recombinant protein, weighing 82 kDa, was purified and confirmed by western blotting. The IgY concentration was determined as 9.5 mg/ml of egg yolk and the purity of the extracted IgY was over 90 %. The results of the ELISA showed that at least 19 ng of pure antibody identified recombinant protein and reacts with it. The challenge test employing IgY and <em>Shigella</em> demonstrated a direct correlation between the survival rate and antibody concentration, with increased concentrations leading to decreased mortality rates. Treatment of mice with 10 mg/kg IgY leads to 80 % survival of the mice against 10 LD50 <em>S. dysenteriae</em>.</p></div><div><h3>Conclusion</h3><p>Our findings suggest that IgY may offer therapeutic potential in treating <em>Shigella</em> infections and combating antibiotic resistance.</p></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"173 ","pages":"Pages 53-60"},"PeriodicalIF":3.2,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141759888","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":"Characteristics and functions of an atypical inflammation-associated GZMK+GZMB+CD8+ T subset in people living with HIV-1","authors":"Liang Zhao ,&nbsp;Huifang Wang ,&nbsp;Yu Zhang ,&nbsp;Yanze Shi ,&nbsp;Chunbao Zhou ,&nbsp;Minrui Yu ,&nbsp;Yanhu Wang ,&nbsp;Liping Zhang ,&nbsp;Zheng Xu ,&nbsp;Ziying Zhang ,&nbsp;Lingyu Gao ,&nbsp;Jiyuan Zhang ,&nbsp;Baopeng Yang ,&nbsp;Huihuang Huang ,&nbsp;Fu-Sheng Wang","doi":"10.1016/j.molimm.2024.07.003","DOIUrl":"10.1016/j.molimm.2024.07.003","url":null,"abstract":"<div><p>HIV-1 chronically infects host CD4⁺ T lymphocytes and further affects a variety of immune cells, including CD8⁺ T cells. In our previous study, by analyzing unbiased high-dimensional single-cell RNA-seq data (scRNA-seq), we found that the frequency of GZMK⁺CD8⁺ T cells expressing granzyme K (GZMK) was increased in people living with HIV-1 (PLWHs). However, the phenotypic and functional characteristics of these cells in chronic HIV-1 infection and their correlation with disease are not well understood. In this study, we conducted a comprehensive analysis of scRNA-seq and matched T-cell receptor repertoire (TCR) sequencing data to delve into the characterizations of GZMK⁺CD8⁺ T cells, which was further validated by flow cytometry. We observed heterogeneity within the GZMK⁺CD8⁺ T cells, which could be further subdivided into a GZMK⁺GZMB^- subset and a GZMK⁺GZMB⁺ subset, with the latter being significantly enriched in PLWHs. The GZMK⁺GZMB⁺ cells are a unique subset within CD8⁺ T cells, characterized by high proliferation, activation, inflammatory response, clone transition, <em>etc</em>., and are one of the differentiation endpoints by pseudotemporal analysis of CD8+αβ T cells. Despite being predominantly composed of effector memory T cells (Tem), similar to the GZMK⁺GZMB^- subset, the GZMK⁺GZMB⁺ subset exhibits differentiation at a later stage than the GZMK⁺GZMB^- subset. We also observed that the frequency/count of GZMK⁺GZMB⁺CD8⁺ T cells was negatively correlated with CD4/CD8 ratio, and positively correlated with HIV DNA, IP-10, and MIG levels in PLWHs. <em>In vitro</em> experiments demonstrate that GZMK can potentiate the stimulatory effects of lipopolysaccharide (LPS) on THP-1 macrophages via the TLR-4 pathway, significantly enhancing the secretion of IP-10, MIG, and MCP-1, as well as increasing the proportion of TNF-α⁺ cells. In conclusion, in PLWHs, GZMK⁺GZMB⁺CD8⁺ T cells are a highly reactive and inflammatory-inducing subset that may be associated with systemic inflammation.</p></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"173 ","pages":"Pages 40-52"},"PeriodicalIF":3.2,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0161589024001238/pdfft?md5=3ee19ed5b1943c932a44ce215916aafa&pid=1-s2.0-S0161589024001238-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141759854","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":"Mycobacterium vaccae attenuates airway inflammation by inhibiting autophagy and activating PI3K/Akt signaling pathway in OVA-induced allergic airway inflammation mouse model","authors":"Huan Xiao ,&nbsp;An-zhou Tang ,&nbsp;Mei-li Xu ,&nbsp;Hong-liu Chen ,&nbsp;Fan Wang ,&nbsp;Chao-Qian Li","doi":"10.1016/j.molimm.2024.07.006","DOIUrl":"10.1016/j.molimm.2024.07.006","url":null,"abstract":"<div><h3>Purpose</h3><p>The etiology of asthma remains elusive, with no known cure. Based on accumulating evidence, autophagy, a self-degradation process that maintains cellular metabolism and homeostasis, participates in the development of asthma. <em>Mycobacterium vaccae</em> vaccine (<em>M. vaccae</em>), an immunomodulatory agent, has previously been shown to effectively alleviate airway inflammation and airway remodeling. However, its therapeutic effect on asthma via the regulation of autophagy remains unknown. Therefore, this study aimed to investigate the impact of <em>M. vaccae</em> in attenuating asthma airway inflammation via autophagy-mediated pathways.</p></div><div><h3>Methods</h3><p>Balb/c mice were used to generate an ovalbumin (OVA)-immunized allergic airway model and were subsequently administered either <em>M. vaccae</em> or <em>M. vaccae</em> + rapamycin (an autophagy activator) prior to each challenge. Next, airway inflammation, mucus secretion, and airway remodeling in mouse lung tissue were assessed via histological analyses. Lastly, the expression level of autophagy proteins LC3B, Beclin1, p62, and autolysosome was determined both in vivo and in vitro, along with the expression level of p-PI3K, PI3K, p-Akt, and Akt in mouse lung tissue.</p></div><div><h3>Results</h3><p>The findings indicated that aerosol inhalation of <em>M. vaccae</em> in an asthma mouse model has the potential to decrease eosinophil counts, alleviate airway inflammation, mucus secretion, and airway remodeling through the inhibition of autophagy. Likewise, <em>M. vaccae</em> could reduce the levels of OVA-specific lgE, IL-5, IL-13, and TNF-α in asthma mouse models by inhibiting autophagy. Furthermore, this study revealed that <em>M. vaccae</em> also suppressed autophagy in IL-13-stimulated BEAS-2B cells. Moreover, <em>M. vaccae</em> may activate the PI3K/Akt signaling pathway in the lung tissue of asthmatic mice.</p></div><div><h3>Conclusion</h3><p>In summary, the present study suggests that <em>M. vaccae</em> may contribute to alleviating airway inflammation and remodeling in allergic asthma by potentially modulating autophagy and the PI3K/Akt signaling pathway. These discoveries offer a promising avenue for the development of therapeutic interventions targeting allergic airway inflammation.</p></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"173 ","pages":"Pages 30-39"},"PeriodicalIF":3.2,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141622471","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":"Endogenous IL-22 contributes to the pathogenesis of salivary gland dysfunction in the non-obese diabetic model of Sjögren’s syndrome","authors":"Fernanda Aragão Felix ,&nbsp;Jing Zhou ,&nbsp;Dongfang Li ,&nbsp;Shoko Onodera ,&nbsp;Qing Yu","doi":"10.1016/j.molimm.2024.06.010","DOIUrl":"10.1016/j.molimm.2024.06.010","url":null,"abstract":"<div><p>Sjӧgren’s syndrome is a systemic autoimmune disease primarily targeting the salivary and lacrimal glands. Our previous investigations have shown that administration of interleukin-22 (IL-22), an IL-10 family cytokine known for its complex and context-dependent effects on tissues, either protective- or detrimental, to salivary glands leads to hypofunction and pathological changes of salivary glands in C57BL/6 mice and in non-obese diabetic (NOD) mice, the latter being a commonly used model of Sjӧgren’s syndrome. This study aims to delineate the pathophysiological roles of endogenously produced IL-22 in the development of salivary gland pathologies and dysfunction associated with Sjӧgren’s disease in the NOD mouse model. Our results reveal that neutralizing IL-22 offered a protective effect on salivary gland function without significantly affecting the immune cell infiltration of salivary glands or the autoantibody production. Blockade of IL-22 reduced the levels of phosphorylated STAT3 in salivary gland tissues of NOD mice, while its administration to salivary glands had the opposite effect. Correspondingly, the detrimental impact of exogenously applied IL-22 on salivary glands was almost completely abrogated by a specific STAT3 inhibitor. Moreover, IL-22 blockade led to a downregulation of protein amounts of Ten-Eleven-Translocation 2, a methylcytosine dioxygenase critical for mediating interferon-induced responses, in salivary gland epithelial cells. IL-22 neutralization also exerted a protective effect on the salivary gland epithelial cells that express high levels of surface EpCAM and bear the stem cell potential, and IL-22 treatment <em>in vitro</em> hampered the survival/expansion of these salivary gland stem cells, indicating a direct negative impact of IL-22 on these cells. In summary, this study has uncovered a critical pathogenic role of the endogenous IL-22 in the pathogenesis of Sjögren’s disease-characteristic salivary gland dysfunction and provided initial evidence that this effect is dependent on STAT3 activation and potentially achieved through fostering Tet2-mediated interferon responses in salivary gland epithelial cells and negatively affecting the EpCAM^high salivary gland stem cells.</p></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"173 ","pages":"Pages 20-29"},"PeriodicalIF":3.2,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141622470","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":"Escherichia coli LTB26 mutant enhances immune responses to rotavirus antigen VP8 in a mouse model","authors":"Qinlin Shi ,&nbsp;Qiujuan Wang ,&nbsp;Yanxi Shen ,&nbsp;Sijing Chen ,&nbsp;Sijie Gan ,&nbsp;Tao Lin ,&nbsp;Fangzhou Song ,&nbsp;Yongping Ma","doi":"10.1016/j.molimm.2024.07.001","DOIUrl":"https://doi.org/10.1016/j.molimm.2024.07.001","url":null,"abstract":"<div><p>Adjuvant is a major supplementary component of vaccines to boost adaptive immune responses. To select an efficient adjuvant from the heat-labile toxin B subunit (LTB) of <em>E. coli</em>, four LTB mutants (numbered LTB26, LTB34, LTB57, and LTB85) were generated by multi-amino acid random replacement. Mice have been intranasally vaccinated with human rotavirus VP8 admixed. Among the four mutants, enzyme-linked immunosorbent assay (ELISA) revealed that LTB26 had enhanced mucosal immune adjuvanticity compared to LTB, showing significantly enhanced immune responses in both serum IgG and mucosal sIgA levels. The 3D modeling analysis suggested that the enhanced immune adjuvanticity of LTB26 might be due to the change of the first LTB α-helix to a β-sheet. The molecular mechanism was studied using transcriptomic and flow cytometric (FCM) analysis. The transcriptomic data demonstrated that LTB26 enhanced immune response by enhancing B cell receptor (BCR) and major histocompatibility complex (MHC) II⁺-related pathways. Furthermore, LTB26 promoted Th1 and Th2-type immune responses which were confirmed by detecting IFN-γ and IL-4 expression levels. Immunohistochemical analysis demonstrated that LTB26 enhanced both Th1 and Th2 type immunity. Therefore, LTB26 was a potent mucosal immune adjuvant meeting the requirement for use in human clinics in the future.</p></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"173 ","pages":"Pages 10-19"},"PeriodicalIF":3.2,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0161589024001214/pdfft?md5=9e27cf0b7a05473499b1bf26b09cb071&pid=1-s2.0-S0161589024001214-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141607792","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":"Inhibition of GBP1 alleviates pyroptosis of human pulmonary microvascular endothelial cells through STAT1/NLRP3/GSDMD pathway","authors":"Yingting Hao,&nbsp;Hongxue Fu,&nbsp;Kaili Li,&nbsp;Xuan Zou,&nbsp;Xin Zhou,&nbsp;Xiyue Tang,&nbsp;Chang Liu,&nbsp;Fachun Zhou","doi":"10.1016/j.molimm.2024.07.005","DOIUrl":"https://doi.org/10.1016/j.molimm.2024.07.005","url":null,"abstract":"<div><p>Restoring and maintaining the function of endothelial cells is critical for acute respiratory distress syndrome (ARDS). Guanylate binding protein 1(GBP1) is proved to elevated in ARDS patients, but its role and mechanism remains unclear. The objective of this study is to investigate the internal mechanism of GBP1 in lung injury. Our study showed that when the LPS and IFN-γ induced human Pulmonary Microvascular Endothelial Cells (HPMECs) injury model was established, cell viability was significantly reduced, and the levels of GBP1 levels and inflammatory factors were significantly increased. When transfection with si-GBP1, low expression of GBP1 promoted cell proliferation and migration, and decreased the expression of downstream inflammatory factors. Furthermore, the inhibition of GBP1 significantly reduced the occurrence of cell pyroptosis and the expression of NLRP3 and STAT1. Our study indicated that GBP1 alleviates endothelial pyroptosis and inflammation through STAT1 / NLRP3/GSDMD signaling pathway, and GBP1 may be a new target in the treatment of lung injury in the future.</p></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"173 ","pages":"Pages 1-9"},"PeriodicalIF":3.2,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141595485","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":"Inhibiting caspase-3/GSDME-mediated pyroptosis ameliorates septic lung injury in mice model","authors":"Hongqian Qin ,&nbsp;Na Lu ,&nbsp;Kai Chen ,&nbsp;Yuhui Huang ,&nbsp;Yan Rui ,&nbsp;Linian Huang ,&nbsp;Qin Gao ,&nbsp;Junfeng Hu","doi":"10.1016/j.molimm.2024.06.007","DOIUrl":"https://doi.org/10.1016/j.molimm.2024.06.007","url":null,"abstract":"<div><p>Acute lung injury is one of the most serious complications of sepsis, which is a common critical illness in clinic. This study aims to investigate the role of caspase-3/ gasdermin-E (GSDME)-mediated pyroptosis in sepsis-induced lung injury in mice model. Cecal ligation (CLP) operation was used to establish mice sepsis-induced lung injury model. Lung coefficient, hematoxylin and eosin staining and transmission electron microscopy were used to observe the lung injury degree. In addition, caspase-3-specific inhibitor Z-DEVD-FMK and GSDME-derived inhibitor AC-DMLD-CMK were used in CLP model, caspase-3 activity, GSDME immunofluorescence, serum lactate dehydrogenase (LDH) and interleukin-6 (IL-6) levels, TUNEL staining, and the expression levels of GSDME related proteins were detected. The mice in CLP group showed the increased expressions of cleaved-caspase-3 and GSDME-N terminal, destruction of lung structure, and the increases of LDH, IL-6, IL-18 and IL-1β levels, which were improved in mice treated with Z-DEVD-FMK or AC-DMLD-CMK. In conclusion, caspase-3/GSDME mediated pyroptosis is involved in the occurrence of sepsis-induced lung injury in mice model, inhibiting caspase-3 or GSDME can both alleviate lung injury.</p></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"172 ","pages":"Pages 96-104"},"PeriodicalIF":3.2,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141483341","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}