Innate Immunity最新文献

{"title":"Preclinical development of the TLR4 antagonist FP12 as a drug lead targeting the HMGB1/MD-2/TLR4 axis in lethal influenza infection.","authors":"Kari Ann Shirey, Alessio Romerio, Mohammed Monsoor Shaik, David S Leake, Charys Palmer, Natalia Skupinska, Jules Paton, Grisha Pirianov, Jorge Cg Blanco, Stefanie N Vogel, Francesco Peri","doi":"10.1177/17534259241313201","DOIUrl":"10.1177/17534259241313201","url":null,"abstract":"<p><strong>Background: </strong>Acute Lung Injuries (ALI) are a severe consequence of influenza-induced cytokine storm that can cause respiratory failure and death. It has been demonstrated that Toll-like Receptor 4 (TLR4) is involved in cytokine storm and that TLR4^-/- mice are protected against ALI. Therefore, TLR4 is a prime target for protection against ALI. FP12 is a known TLR4 antagonist that reduces TLR4-dependent immune activation and it is a promising lead compound for the treatment of innate immunity related pathologies.</p><p><strong>Objectives: </strong>We present here the preclinical development of FP12 as an anti-inflammatory lead compound acting on influenza-induced ALI.</p><p><strong>Methods: </strong><i>In vitro:</i> We pre-treated THP-1 cells with FP12 (10 μM) for 0.5 h, then exposed to LPS (100 ng/ml) for 0 to 16 h. In some experiments, cells were simultaneously incubated with FP12 and LPS, or FP12 was added 30 min after LPS. Cytokine levels were measured by Western blot and ELISA assays. <i>In vivo:</i> WT C57BL/6J mice were infected with mouse-adapted influenza virus (PR8). Two days after infection, mice received either vehicle, FP7 (200 µg/mouse), or FP12 (200 µg/mouse) once daily (Day 2 to Day 6). Mice were monitored daily for survival for 14 days. Data were collected through histological staining, qRT-PCR, and ELISA assay.</p><p><strong>Results: </strong>FP12 treatment inhibited both LPS- and HMGB1-induced TLR4 intracellular pathways (MyD88 and TRIF) leading to significantly reduced levels of a variety of proinflammatory cytokines including Type I interferon (IFN-β), highlighting its effectiveness in controlling proinflammatory protein production and reducing inflammation. FP12 protected mice therapeutically from influenza virus-induced lethality and reduced both cytokine gene expression and High Mobility Group Box 1 (HMGB1) levels in the lungs as well as ALI.</p><p><strong>Conclusion: </strong>FP12 can antagonize TLR4 activation in vitro and protects mice from severe influenza infection, most likely by reducing the TLR4-dependent cytokine storm mediated by danger-associated molecular patterns (DAMPs).</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"31 ","pages":"17534259241313201"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11877469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143541972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mutation within the transmembrane domain of oxidized low-density lipoprotein receptor 1 influences oxidized low-density lipoprotein-induced signal transduction.","authors":"Zhen Ma, Ran Xu, Jing Lu, Xiong Huang, Hao Jia, Zhiwen Ding, Jie Yuan, Yunzeng Zou","doi":"10.1177/17534259251350447","DOIUrl":"https://doi.org/10.1177/17534259251350447","url":null,"abstract":"<p><p>ObjectiveTo investigate the important active sites within the NTFs to affect the <i>in vitro</i> interaction of oxidized low-density lipoprotein (ox-LDL) with its receptor, OLR1.MethodsSimulation analysis online was performed to generate various OLR1 chimeras, truncation mutants, and site-specific mutations. They were transfected in COS-7 cells and subjected to ox-LDL stimulations to observe the different reactions. Immunoprecipitation-mass spectrometry (IP-MS) was performed to show what proteins combined with OLR1 mutants in reaction to ox-LDL. Lipid uptake in human monocytes (THP-1) originated foam cells overexpressing somatic mutant of OLR1 were also determined. Further studies focusing on these regions were conducted using truncation mutants and site-specific mutants such as G43A, V44A, L45A, C46A, and L47A.ResultsAmino acids within the TM were highly conserved, spanning amino acids 35 to 57. The induction of intracellular p-ERK1/2 in response to ox-LDL stimulation was highly promoted in Chimera 3 possessing the TM from OLR1 like OLR1/WT (<i>p</i> < 0.05). Sequence alignment revealed two conserved regions within the TM of OLR1, Leu45-Cys46-Leu47 and Val55-Leu56-Gly57. Western blot showed that most of the TM changes ablated ERK1/2 activation in response to ox-LDL stimulation (<i>p</i> < 0.05). One human somatic mutation at L45F revealed significantly lower p-ERK1/2 levels with enhanced intake of ox-LDL in THP-1-derived foam cells than the control cells (<i>p</i> < 0.05). L45A and C46A molecular complexes were identified. After ox-LDL stimulation, these underlined interactions with keratins, namely KRT2 and KRT6A.ConclusionThese findings emphasize the vital role of the TM in the interactions between OLR1 and ox-LDL and point to an exciting possibility that signal transduction induced by ox-LDL through its receptor OLR1 may involve complex interactions with cytoskeletal proteins.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"31 ","pages":"17534259251350447"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tracking mucosal innate immune responses to three influenza A virus strains in a highly translational pig model using nasopharyngeal swabs.","authors":"Helena A Laybourn, Charlotte Kristensen, Anders G Pedersen, Louise Brogaard, Sophie George, Betina L Henriksen, Chrysillis H Polhaus, Ramona Trebbien, Lars E Larsen, Kerstin Skovgaard","doi":"10.1177/17534259251331385","DOIUrl":"10.1177/17534259251331385","url":null,"abstract":"<p><p>BackgroundFour influenza pandemics have occurred during the past 100 years, and new variants of influenza viruses will continue to emerge. The nasal mucosa acts as the primary site of exposure to influenza A virus (IAV) infection, but viral recognition and host immune responses in the nasal mucosa are still poorly understood.ObjectivesThis study aimed to evaluate the utility of non-invasive nasopharyngeal swabs for longitudinal monitoring of mucosal immune responses in pigs experimentally challenged with two swine-adapted and one human-adapted IAV. By tracking antiviral immune responses from disease onset to recovery, we sought to assess the feasibility of this method for capturing dynamic changes in viral load and host responses across different IAV strains.MethodsForty-two IAV-negative pigs were divided into four groups and housed separately for infection studies. Viral and host RNA from nasopharyngeal swabs was analyzed using microfluidic qPCR, while statistical analysis was performed with a Bayesian approach in R. Additionally, immunohistochemical staining was used to assess MUC5AC expression in the nasal mucosa of infected pigs.ResultsRNA was successfully isolated from nasopharyngeal swabs, enabling gene expression analysis to monitor innate immune responses to IAV infection. A classical innate antiviral immune response was demonstrated after the three virus infections including expression of pattern recognition receptors (PRRs), transcription factors, interferons (IFNs), interferon-stimulated genes (ISGs), cytokines, and chemokines. The kinetics and magnitude of immune responses varied between infections, with notable downregulation of mucins following infection with the Danish swine-adapted isolate. Further, the Danish isolate induced a fast but transient IFN-mediated response concurrent with high expression of cytokines and chemokines, while the other swine-adapted Mexican isolate induced a prolonged immune response of ISGs, cytokines, and chemokines.ConclusionThis study highlights the significance of highly translational nasopharyngeal swabs as a non-invasive method for assessing mucosal antiviral immune responses. Utilizing microfluidic mRNA analysis, we gained valuable insights into antiviral mucosal responses across 216 swab samples collected from viral inoculation through recovery in three distinct influenza virus infections.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"31 ","pages":"17534259251331385"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11960188/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipopolysaccharide preconditioning augments the antibacterial activity of renal macrophages and ameliorates acute kidney injury caused by <i>Staphylococcus aureus</i> bacteremia in mice.","authors":"Keiko Tanoue, Manabu Kinoshita, Bradley M Kearney, Seigo Ito, Hiroyasu Goto, Aoi Yamashiro, Tsugumi Fukunaga, Hiroki Sato, Kazuma Mori, Koji Kuwata, Hidehito Matsubara, Azusa Kato, Masahiro Nakashima, Hiroyuki Nakashima, Toshihiko Imakiire, Naoki Oshima","doi":"10.1177/17534259251335770","DOIUrl":"10.1177/17534259251335770","url":null,"abstract":"<p><p>IntroductionRepeated injections of low-dose lipopolysaccharide (LPS preconditioning) augment the antibacterial activity of liver macrophages. In this study, a mouse model of acute kidney injury (AKI) induced by <i>Staphylococcus aureus (S. aureus)</i> bacteremia was used to investigate the effects of LPS preconditioning on renal macrophages.MethodsEight-week-old C57BL/6J mice were preconditioned with either low-dose LPS (5 μg/kg) or the vehicle for three consecutive days. Kidney immune cells were isolated, and the antibacterial activity of renal macrophages was assessed by pHrodo^TM-labeled <i>S. aureus in vitro</i>. Twenty-four hours after the last LPS injection, the mice were intravenously challenged with <i>S. aureus</i> (2 × 10⁷ CFU) and their renal function was evaluated to identify the changes.ResultsMouse renal macrophages exhibited a weak antibacterial activity against <i>S. aureus</i> compared with the liver and spleen macrophages. LPS preconditioning elevated the count of F4/80^low CD11b^high bone marrow-derived macrophages (BMDM) and augmented their antibacterial activities in the mouse kidney. It also enhanced the antibacterial activity of F4/80^high CD11b^low tissue-resident macrophages (TRM) without altering their abundance. LPS preconditioning lowered the bacterial propagation in the kidney in the challenged mice and ameliorated sepsis-associated AKI compared with the control. LPS preconditioning upregulated the CD80/CD206 expression (M1/M2) ratio in BMDMs in the kidney before bacterial challenge and reduced their M1/M2 ratio following <i>S. aureus</i> challenge compared with the control.ConclusionLPS preconditioning enhanced the antibacterial activity of the renal macrophages against <i>S. aureus</i> and suppressed the excessive activation of M1 macrophages following <i>S. aureus</i> challenge, resulting in the amelioration of AKI caused by <i>S. aureus</i> bacteremia.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"31 ","pages":"17534259251335770"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12035103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143978415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inherent immunity and adaptive immunity: Mechanism and role in AECOPD.","authors":"Linguangjin Wu, Erxin Zhang, Yadan Tu, Yong Chen, Chenghu Wang, Yi Ren, Bangjiang Fang","doi":"10.1177/17534259251322612","DOIUrl":"10.1177/17534259251322612","url":null,"abstract":"<p><p>Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is the leading cause of hospitalization and mortality in COPD patients. The occurrence of antibiotic resistance and the progression of non-infectious diseases contribute to poor patient outcomes. Thus, a comprehensive understanding of the mechanisms underlying AECOPD is essential for effective prevention. It is widely acknowledged that the immune system plays a fundamental role in pathogen clearance and the development of inflammation. Immune dysregulation, either due to deficiency or hyperactivity, has been implicated in AECOPD pathogenesis. Therefore, the purpose of this review is to investigate the possible mechanisms underlying dysregulated immune function and disease progression in COPD patients, specifically focusing on the innate and adaptive immune responses. The ultimate aim is to provide new insights for clinical prevention and treatment strategies targeting AECOPD.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"31 ","pages":"17534259251322612"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11869301/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-Rheumatic potential of biological DMARDS and protagonistic role of bio-markers in early detection and management of rheumatoid arthritis.","authors":"Muhammad Riaz, Ghulam Rasool, Ruhamah Yousaf, Hina Fatima, Naveed Munir, Hasan Ejaz","doi":"10.1177/17534259251324820","DOIUrl":"10.1177/17534259251324820","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) is a chronic inflammatory disease that primarily affects the synovial joint linings, resulting in progressive disability, increased mortality, and considerable economic costs. Early treatment with disease-modifying antirheumatic medications (DMARDs) can significantly improve the overall outlook for people with RA. Contemporary pharmaceutical interventions, encompassing standard, biological, and emerging small molecule disease- modifying anti-rheumatic medications continue to be the cornerstone of RA management, with substantial advancements made in the pursuit of achieving remission from the disease and preventing joint deformities. Nevertheless, a substantial segment of individuals with RA do not experience a satisfactory response to existing treatments, underscoring the pressing need for novel therapeutic options. Biologic DMARDs are among the therapy choices. Non-tumor necrosis factor inhibitors (Non-TNFi) such as abatacept, rituximab, tocilizumab, and sarilumab are examples, as are anti-tumor necrosis factor (TNF) medications such as infliximab, adalimumab, etanercept, golimumab, and certolizumab pegol. More recent biomarkers have emerged and showed usefulness in the early detection of RA. These biomarkers, often referred to simply as \"biomarkers\", are quantifiable indicators of normal or pathologic processes, and they can also gauge treatment response. The assessment of RA treatment response typically combines patient-reported outcomes, physical evaluations, and laboratory findings, as there isn't a single biomarker that has proven sufficient for measuring disease activity. This review explores the usage of biologic DMARDs as a therapeutic approach for RA, as well as the biomarkers typically used for RA early diagnosis, prognosis prediction, and disease activity evaluation.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"31 ","pages":"17534259251324820"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912179/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143648507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRPM2 deficiency contributes to M2b macrophage polarization via the PI3K/AKT/CREB pathway in murine sepsis.","authors":"Yanping Shen, Rana Dhar, Jujun Liu, Shenghui Hong, Huifang Tang, Xiaowei Qian","doi":"10.1177/17534259251343377","DOIUrl":"10.1177/17534259251343377","url":null,"abstract":"<p><p>BackgroundPrevious studies suggest that transient receptor potential melastatin 2 (TRPM2) plays a protective role in sepsis by enhancing bacterial clearance. This effect is mediated through the modulation of macrophage phenotypic changes, which strengthen the immune response against infection. However, the specific role and underlying mechanism of TRPM2 in macrophage polarization during sepsis remain unclear.MethodCecal ligation and puncture (CLP) was used to establish a mouse sepsis model, and bone marrow-derived macrophages (BMDMs) and peritoneal macrophages were prepared from C57BL/6 wild-type and TRPM2 knockout (<i>trpm</i>2^-/-) mice. IPI549 was utilized as a specific inhibitor of PI3K. Macrophage polarization, bactericidal ability, and the PI3K/protein kinase B (AKT)/cyclic adenosine monophosphate response element-binding protein signaling pathway were assessed. In addition, survival rate, bacterial burden, lung wet/dry weight ratio, lung and liver injury scores, and cytokine levels were measured in CLP-induced septic mice.ResultsIn lipopolysaccharide (LPS)-stimulated BMDMs, <i>trpm</i>2 deficiency increased the expression of characteristic markers associated with the M2b phenotype, reduced the bactericidal ability, and activated the PI3K/AKT/CREB signaling pathway. Consequently, both <i>trpm</i>2^-/- BMDMs and <i>trpm2</i>^-/- mice exhibited impaired bactericidal clearance during CLP-induced sepsis. Furthermore, IPI549 attenuated TRPM2 deletion-induced M2b polarization and restored the bactericidal function of BMDMs. Notably, IPI549 preconditioning reversed the increased susceptibility of the <i>trpm</i>2^-/- mice to sepsis. The 7-day mortality rate was 92% in <i>trpm</i>2^-/- mice, compared to 42% in IPI549-pretreated <i>trpm</i>2^-/- mice. Moreover, IPI549-treated mice exhibited improved lung wet/dry ratios, reduced lung and liver injury scores, reversed M2b polarization and decreased bacterial load.ConclusionThe PI3K/AKT/CREB pathway mediates the effect of TRPM2 by inhibiting M2b macrophage polarization and promoting bacterial clearance during sepsis.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"31 ","pages":"17534259251343377"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12102566/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144127398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The imbalance of circulating PD-L1-expressing non-classical/ classical monocytes is involved in immunocompromised host related pulmonary opportunistic infection.","authors":"Danhong Zhou, Yujia Jin, Yifan Jin, Yu Shen, Qiuxia Qu, Cheng Chen","doi":"10.1177/17534259251316152","DOIUrl":"10.1177/17534259251316152","url":null,"abstract":"<p><p>The application of biological therapy and glucocorticoids in Auto-immune diseases (AID) patients will cause immunocompromised host (ICH) prone to infection. And monocytes play a key role in both innate and adaptive immune responses. We aimed to investigate the changes of circulating monocyte subsets in AID or AID-ICH patients with pulmonary infection. The subgroups and PD-L1 expression of monocytes were measured by flow cytometry in healthy individuals (HC), new-onset AID patients (AID cohort) and AID-ICH patients with pulmonary opportunistic infection (AID-ICH cohort). Flow cytometry analysis was used to determine the distribution of monocyte subsets, including classical monocytes (CL, CD14⁺⁺CD16^-), intermediate monocytes (ITM, CD14⁺⁺CD16⁺) and non-classical monocytes (NC, CD14^+/-CD16⁺⁺), as well as the dynamic change of PD-L1 ⁺cluster among monocyte subsets. Among total monocyte, AID-ICH displayed decreased CL subset along with increased NC subset compared to HCs and AID. Regarding PD-L1 ⁺monocytes, although CL subset constituted the majority of that in HCs, AIDs and AID-ICHs, imbalance of NC/CL within PD-L1 ⁺monocytes was only noticed in AID-ICHs (<i>P</i> < 0.05). Furthermore, when AID subjects were developed into immunocompromised status (ICH), PD-L1 ⁺cluster in CL was minorly decreased (<i>P</i> > 0.05). Clinically, the lower ratio of PD-L1 ⁺cluster among CL subset (<i>P</i> < 0.05) and the less differentiated CL in PD-L1 ⁺monocytes (<i>P</i> < 0.05) was more likely to leaded to disease progression. The imbalance of circulating NC/CL subset was remarkable in immunocompromised host with pulmonary opportunistic infection, especially involvement of PD-L1⁺ cluster, which served as a potential biomarker in clinical practice.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"31 ","pages":"17534259251316152"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11774481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging roles of SLAMF7 in immune cells and related diseases.","authors":"Zheng Zhang, Ying Zhang, Zeyu Chen, Lin Xia","doi":"10.1177/17534259251326700","DOIUrl":"10.1177/17534259251326700","url":null,"abstract":"<p><p>Immune cells are heterogeneous and perform different functions in different microenvironment, thus playing different roles in different stages of diseases. Studies have shown that immune cells are involved in the pathogenesis of many diseases, and there is a causal association of immune cells with disease states. Signaling Lymphocyte Activation Molecule family (SLAMF) members are a newly appreciated group of specific receptors that are mainly expressed in immune cells and whose role is to regulate the function of immune cells. SLAMF7, also known as CD319, has been widely reported in multiple myeloma, and in recent years, more and more studies have shown that SLAMF7 is widely involved in the function of immune cells and the progression of breast cancer, acquired immune deficiency syndrome, systemic lupus erythematosus and other immune cells-related diseases. However, the mechanisms underlying the regulatory role of SLAMF7 on immune cells, and the impact on the progression of immune cells-related diseases remain poorly elucidated. In this review, we summarize current knowledge about the role of SLAMF7 in immune cells and related diseases such as cancer, infectious disease, autoimmune disease and atherosclerosis, and the therapeutic strategy targeting SLAMF7 is also described. By better understanding the role and regulation of SLAMF7, we hope to provide new insights and directions for improving the diagnosis and treatment of inflammation.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"31 ","pages":"17534259251326700"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912174/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143648513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of killer immunoglobulin-like receptor genotypes and haplotypes with acute lymphoblastic leukemia risk.","authors":"Jameel Al-Tamimi, Suliman Alomar, Ali Aljuaimlani, Lamjed Mansour","doi":"10.1177/17534259251314774","DOIUrl":"10.1177/17534259251314774","url":null,"abstract":"<p><strong>Background: </strong>Killer immunoglobulin-like receptors (KIRs) are key molecules used by natural killer (NK) cells to interact with target cells. These receptors exhibit extensive genotypic polymorphism which has been associated with varying outcomes in immune responses against diseases. This study aimed to investigate the relationships between <i>KIR</i> genotypes and haplotypes with acute lymphoblastic leukemia (ALL) in Saudi patients.</p><p><strong>Methods: </strong>A total of 259 Saudi subjects including 145 cases of acute lymphoblastic leukemia (ALL) and 114 healthy controls living in Riyadh were genotyped for 16 <i>KIR</i> genes and the two <i>HLA-C1</i> and <i>-C2</i> allotypes using PCR-SSP genotyping method.</p><p><strong>Results: </strong>A significant high frequency of the two inhibitory <i>KIR</i> genes; <i>2DL1</i> (OR = 2.4; <i>p</i> < 0.0001) and <i>3DL1</i>(OR = 10.87; <i>p</i> = 0.0068) in ALL compared to healthy group was observed. In contrast, the activating <i>2DS4</i> gene was significantly higher in healthy controls (OR = 0.15, <i>p</i> < 0.0001) compared to ALL patients. Haplotype analysis shows that BX haplogroup was strongly associated with the occurrence of ALL (OR = 4.39; <i>p</i> < 0.0001). Further combinatory analysis of <i>KIR</i> genes with their <i>HLA-C1</i> and <i>-C2</i> ligands demonstrated strong statistically protective effect of the <i>2DS1-C2</i> combination from ALL (OR = 0.06; <i>p</i> = 0.0003).</p><p><strong>Conclusion: </strong>This study presents strong evidence supporting the connection between certain <i>KIR</i> genotypes, haplotypes, and <i>KIR-HLA</i> combinations with acute ALL in the Saudi population. The heightened occurrence of inhibitory <i>KIR</i> genes (<i>2DL1</i> and <i>3DL1</i>) and the BX haplotype in ALL patients indicates a possible involvement of these genetic variability with the dysfunctional of NK cells in the context of ALL disease.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"31 ","pages":"17534259251314774"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11774482/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}