Clinical and experimental immunology最新文献_第10页

Female-specific enhancement of eosinophil recruitment and activation in a type 2 innate inflammation model in the lung. 在肺部 2 型先天性炎症模型中，嗜酸性粒细胞招募和活化的女性特异性增强。

IF 3.4 3区医学

Clinical and experimental immunology Pub Date : 2024-03-12 DOI: 10.1093/cei/uxad100

Rami Karkout, Véronique Gaudreault, Lydia Labrie, Haya Aldossary, Noelia Azalde Garcia, Jichuan Shan, Elizabeth D Fixman

{"title":"Female-specific enhancement of eosinophil recruitment and activation in a type 2 innate inflammation model in the lung.","authors":"Rami Karkout, Véronique Gaudreault, Lydia Labrie, Haya Aldossary, Noelia Azalde Garcia, Jichuan Shan, Elizabeth D Fixman","doi":"10.1093/cei/uxad100","DOIUrl":"10.1093/cei/uxad100","url":null,"abstract":"A sex disparity in asthma prevalence and severity exists in humans. Multiple studies have highlighted the role of innate cells in shaping the adaptive immune system in chronic asthma. To explore the sex bias in the eosinophilic response, we delivered IL-33 to the lungs of mice and delineated the kinetics by which the inflammatory response was induced. Our data demonstrate that females recruited more eosinophils capable of responding to IL-33. Eosinophil activation occurred selectively in the lung tissue and was enhanced in females at all time points. This increase was associated with increased ex vivo type 2 cytokine and chemokine production and female-specific expansion of group 2 innate lymphoid cells lacking expression of the killer-cell lectin-like receptor G1. Our findings suggest that the enhanced eosinophilic response in females is due, firstly, to a greater proportion of eosinophils recruited to the lungs in females that can respond to IL-33; and secondly, to an enhanced production of type 2 cytokines in females. Our data provide insight into the mechanisms that guide the female-specific enhancement of eosinophil activation in the mouse and form the basis to characterize these responses in human asthmatics.","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":"13-24"},"PeriodicalIF":3.4,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10929703/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10107586","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}

引用次数: 0

The CXCL10-CXCR3 axis plays an important role in Kawasaki disease. CXCL10-CXCR3轴在川崎病中起重要作用。

IF 3.4 3区医学

Clinical and experimental immunology Pub Date : 2024-03-12 DOI: 10.1093/cei/uxad125

Sho Hosaka, Kazuo Imagawa, Yusuke Yano, Lisheng Lin, Junko Shiono, Miho Takahashi-Igari, Hideki Hara, Daisuke Hayashi, Hironori Imai, Atsushi Morita, Hiroko Fukushima, Hidetoshi Takada

引用次数: 0

FGL1 in plasma extracellular vesicles is correlated with clinical stage of lung adenocarcinoma and anti-PD-L1 response. 血浆细胞外囊泡中的FGL1与肺腺癌的临床分期和抗PD-L1反应相关。

IF 4.6 3区医学

Clinical and experimental immunology Pub Date : 2024-03-12 DOI: 10.1093/cei/uxad137

Yuchen Zhang, Kunpeng Zhang, Haoyu Wen, Di Ge, Jie Gu, Chunyi Zhang

{"title":"FGL1 in plasma extracellular vesicles is correlated with clinical stage of lung adenocarcinoma and anti-PD-L1 response.","authors":"Yuchen Zhang, Kunpeng Zhang, Haoyu Wen, Di Ge, Jie Gu, Chunyi Zhang","doi":"10.1093/cei/uxad137","DOIUrl":"10.1093/cei/uxad137","url":null,"abstract":"Fibrinogen-like protein-1 (FGL1) is confirmed a major ligand of lymphocyte activation gene-3 which could inhibit antigen-mediated T-cell response and evade immune supervision. Although hepatocytes secrete large amounts of FGL1, its high expression also be detected in solid tumors such as lung cancer, leading to a poor efficacy of immune checkpoint inhibitors therapy. Here we reported that FGL1 was overexpressed in lung adenocarcinoma (LUAD) but not in lung squamous cell carcinoma. However, FGL1 in tissue and plasma can only distinguish LUAD patients from healthy donors and cannot correlate with clinical Tumor Node Metastasis (TNM) stage. Using lung cancer cell lines, we confirmed that FGL1 can be detected on extracellular vesicles (EVs) and we established a method using flow cytometry to detect FGL1 on the surface of EVs, which revealed that FGL1 could be secreted via EVs. Both animal model and clinical samples proved that plasma FGL1 in EVs would increase when the tumor was loaded. The level of FGL1 in plasma EVs was correlated with clinical TNM stage and tumor size, and a higher level indicated non-responsiveness to anti-programmed cell death ligand 1 (anti-PD-L1) immunotherapy. Its effect on tumor progression and immune evasion may be achieved by impairing the killing and proliferating capacities of CD8+ T cells. Our result demonstrates that FGL1 levels in plasma EVs, but not total plasma FGL1, could be a promising biomarker that plays an important role in predicting anti-PD-L1 immune therapy in LUAD and suggests a new strategy in LUAD immunotherapy.","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":"68-79"},"PeriodicalIF":4.6,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10929704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139037406","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}

引用次数: 0

Enhanced efficacy of the novel recombinant clone VasSF in a mouse model of antineutrophil cytoplasmic antibody-associated vasculitis. 新型重组克隆 VasSF 在抗中性粒细胞胞浆抗体相关性血管炎小鼠模型中的疗效增强。

IF 4.6 3区医学

Clinical and experimental immunology Pub Date : 2024-03-12 DOI: 10.1093/cei/uxad140

Minako Koura, Yosuke Kameoka, Fukuko Kishi, Yoshio Yamakawa, Fuyu Ito, Ryuichi Sugamata, Yuko Doi, Kazuko Uno, Toshinori Nakayama, Takashi Miki, Hiroshi Nakajima, Kazuo Suzuki, Osamu Suzuki

{"title":"Enhanced efficacy of the novel recombinant clone VasSF in a mouse model of antineutrophil cytoplasmic antibody-associated vasculitis.","authors":"Minako Koura, Yosuke Kameoka, Fukuko Kishi, Yoshio Yamakawa, Fuyu Ito, Ryuichi Sugamata, Yuko Doi, Kazuko Uno, Toshinori Nakayama, Takashi Miki, Hiroshi Nakajima, Kazuo Suzuki, Osamu Suzuki","doi":"10.1093/cei/uxad140","DOIUrl":"10.1093/cei/uxad140","url":null,"abstract":"Based on the efficacy of intravenous immunoglobulin (IVIg) for the treatment of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), we developed a recombinant single-chain-fragment variable clone, VasSF, therapeutic against AAV in a mouse model (SCG/Kj mice). VasSF is thought to bind to vasculitis-associated apolipoprotein A-II (APOA2) as a target molecule. VasSF is a promising new drug against AAV, but difficulties in the yield and purification of VasSF remain unresolved. We produced monomers of new VasSF molecules by modifying the plasmid structure for VasSF expression and simplifying the purification method using high-performance liquid chromatography. We compared the therapeutic effects between 5-day continuous administration of the monomers, as in IVIg treatment, and single shots of 5-day-equivalent doses. We also evaluated the life-prolonging effect of the single-shot treatment. Two-dimensional western blots were used to examine the binding of VasSF to APOA2. Our improved manufacturing method resulted in a 100-fold higher yield of VasSF than in our previous study. Monomerization of VasSF stabilized its efficacy. Single shots of a small amount (1/80 000 of IVIg) produced sufficient therapeutic effects, including decreased glomerular crescent formation, a decreasing trend of serum ANCA against myeloperoxidase (MPO-ANCA), decreases in multiple proinflammatory cytokines, and a trend toward prolonged survival. Two-dimensional western blots confirmed the binding of VasSF to APOA2. The newly produced pure VasSF monomers are stable and therapeutic for AAV with a single low-dose injection, possibly by removing vasculitis-associated APOA2. Thus, the new VasSF described herein is a promising drug against AAV.","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":"55-67"},"PeriodicalIF":4.6,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10929700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139073496","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}

引用次数: 0

Sicilian semi- and supercentenarians: age-related Tγδ cell immunophenotype contributes to longevity trait definition. 西西里半百岁老人和超百岁老人：与年龄相关的 Tγδ 细胞免疫表型有助于界定长寿特征。

IF 4.6 3区医学

Clinical and experimental immunology Pub Date : 2024-03-12 DOI: 10.1093/cei/uxad132

Mattia Emanuela Ligotti, Giulia Accardi, Anna Aiello, Anna Calabrò, Calogero Caruso, Anna Maria Corsale, Francesco Dieli, Marta Di Simone, Serena Meraviglia, Giuseppina Candore

{"title":"Sicilian semi- and supercentenarians: age-related Tγδ cell immunophenotype contributes to longevity trait definition.","authors":"Mattia Emanuela Ligotti, Giulia Accardi, Anna Aiello, Anna Calabrò, Calogero Caruso, Anna Maria Corsale, Francesco Dieli, Marta Di Simone, Serena Meraviglia, Giuseppina Candore","doi":"10.1093/cei/uxad132","DOIUrl":"10.1093/cei/uxad132","url":null,"abstract":"The immune system of semi- (from ≥105 to <110 years old) and supercentenarians (≥110 years old), i.e. oldest centenarians, is thought to have characteristics that allow them to reach extreme longevity in relatively healthy status. Thus, we investigated variations of the two principal subsets of Tγδ, Vδ1, and Vδ2, and their functional subsets using the markers defining Tαβ cells, i.e. CD27, CD45RA, in a cohort of 28 women and 26 men (age range 19-110 years), including 11 long-living individuals (from >90 years old to<105 years old), and eight oldest centenarians (≥105 years old), all of them were previously analysed for Tαβ and NK cell immunophenotypes on the same blood sample collected on recruitment day. Naïve Vδ1 and Vδ2 cells showed an inverse relationship with age, particularly significant for Vδ1 cells. Terminally differentiated T subsets (TEMRA) were significantly increased in Vδ1 but not in Vδ2, with higher values observed in the oldest centenarians, although a great heterogeneity was observed. Both naïve and TEMRA Vδ1 and CD8+ Tαβ cell values from our previous study correlated highly significantly, which was not the case for CD4+ and Vδ2. Our findings on γδ TEMRA suggest that these changes are not unfavourable for centenarians, including the oldest ones, supporting the hypothesis that immune ageing should be considered as a differential adaptation rather than a general immune alteration. The increase in TEMRA Vδ1 and CD8+, as well as in NK, would represent immune mechanisms by which the oldest centenarians successfully adapt to a history of insults and achieve longevity.","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":"1-12"},"PeriodicalIF":4.6,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10929699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138799481","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}

引用次数: 0

Gene expression analysis revealed downregulation of complement receptor 1 in clonal B cells in cold agglutinin disease. 基因表达分析显示，冷凝集素病的克隆 B 细胞中补体受体 1 下调。

IF 4.6 3区医学

Clinical and experimental immunology Pub Date : 2024-03-12 DOI: 10.1093/cei/uxad135

Agnieszka Małecka, Ingunn Østlie, Gunhild Trøen, Jędrzej Małecki, Jan Delabie, Anne Tierens, Ludvig A Munthe, Sigbjørn Berentsen, Geir E Tjønnfjord

{"title":"Gene expression analysis revealed downregulation of complement receptor 1 in clonal B cells in cold agglutinin disease.","authors":"Agnieszka Małecka, Ingunn Østlie, Gunhild Trøen, Jędrzej Małecki, Jan Delabie, Anne Tierens, Ludvig A Munthe, Sigbjørn Berentsen, Geir E Tjønnfjord","doi":"10.1093/cei/uxad135","DOIUrl":"10.1093/cei/uxad135","url":null,"abstract":"Cold agglutinin disease (CAD) is a rare B-cell lymphoproliferative disorder of the bone marrow, manifested by autoimmune hemolytic anemia caused by binding of monoclonal IgM autoantibodies to the I antigen. Underlying genetic changes have previously been reported, but their impact on gene expression profile has been unknown. Here, we define differentially expressed genes in CAD B cells. To unravel downstream alteration in cellular pathways, gene expression by RNA sequencing was undertaken. Clonal B-cell samples from 12 CAD patients and IgM-expressing memory B cells from 4 healthy individuals were analyzed. Differential expression analysis and filtering resulted in 93 genes with significant differential expression. Top upregulated genes included SLC4A1, SPTA1, YBX3, TESC, HBD, AHSP, TRAF1, HBA2, RHAG, CA1, SPTB, IL10, UBASH3B, ALAS2, HBA1, CRYM, RGCC, KANK2, and IGHV4-34. They were upregulated at least 8-fold, while complement receptor 1 (CR1/CD35) was downregulated 11-fold in clonal CAD B cells compared to control B cells. Flow cytometry analyses further confirmed reduced CR1 (CD35) protein expression by clonal CAD IgM+ B cells compared to IgM+ memory B cells in controls. CR1 (CD35) is an important negative regulator of B-cell activation and differentiation. Therefore, reduced CR1 (CD35) expression may increase activation, proliferation, and antibody production in CAD-associated clonal B cells.","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":"45-54"},"PeriodicalIF":4.6,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10929701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138828441","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}

引用次数: 0

Shift in the B cell subsets between children with type 1 diabetes and/or celiac disease. 1 型糖尿病和/或乳糜泻患儿 B 细胞亚群的变化。

IF 4.6 3区医学

Clinical and experimental immunology Pub Date : 2024-03-12 DOI: 10.1093/cei/uxad136

Andrea Tompa, Maria Faresjö

{"title":"Shift in the B cell subsets between children with type 1 diabetes and/or celiac disease.","authors":"Andrea Tompa, Maria Faresjö","doi":"10.1093/cei/uxad136","DOIUrl":"10.1093/cei/uxad136","url":null,"abstract":"Our purpose was to characterize the pattern of B cell subsets in children with a combined diagnosis of type 1 diabetes (T1D) and celiac disease (C) since children with single or double diagnosis of these autoimmune diseases may differ in peripheral B cell subset phenotype patterns. B cells were analyzed with flow cytometry for the expression of differentiation/maturation markers to identify transitional, naive, and memory B cells. Transitional (CD24hiCD38hiCD19+) and memory Bregs (mBregs; CD24hiCD27+CD19+, CD1d+CD27+CD19+, and CD5+CD1d+CD19+) were classified as B cells with regulatory capacity. Children with a combined diagnosis of T1D and C showed a pattern of diminished peripheral B cell subsets. The B cells compartment in children with combined diagnosis had higher percentages of memory B subsets and Bregs, including activated subsets, compared to children with either T1D or C. Children with combined diagnosis had a lower percentage of naive B cells (CD27-CD19+; IgD+CD19+) and an increased percentage of memory B cells (CD27+CD19+; IgD-CD19+). A similar alteration was seen among the CD39+ expressing naive and memory B cells. Memory Bregs (CD1d+CD27+CD19+) were more frequent, contrary to the lower percentage of CD5+ transitional Bregs in children with a combined diagnosis. In children with either T1D or C, the peripheral B cell compartment was dominated by naive cells. Differences in the pattern of heterogeneous peripheral B cell repertoire subsets reflect a shifting in the B cell compartment between children with T1D and/or C. This is an immunological challenge of impact on the pathophysiology of these autoimmune diseases.","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":"36-44"},"PeriodicalIF":4.6,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10929695/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138884612","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}

引用次数: 0

Defining the cross-reactivity between peanut allergens Ara h 2 and Ara h 6 using monoclonal antibodies. 使用单克隆抗体确定花生过敏原 Ara h 2 和 Ara h 6 之间的交叉反应。

IF 3.4 3区医学

Clinical and experimental immunology Pub Date : 2024-03-12 DOI: 10.1093/cei/uxae005

Orlee Marini-Rapoport, Monica L Fernández-Quintero, Tarun Keswani, Guangning Zong, Jane Shim, Lars C Pedersen, Geoffrey A Mueller, Sarita U Patil

{"title":"Defining the cross-reactivity between peanut allergens Ara h 2 and Ara h 6 using monoclonal antibodies.","authors":"Orlee Marini-Rapoport, Monica L Fernández-Quintero, Tarun Keswani, Guangning Zong, Jane Shim, Lars C Pedersen, Geoffrey A Mueller, Sarita U Patil","doi":"10.1093/cei/uxae005","DOIUrl":"10.1093/cei/uxae005","url":null,"abstract":"In peanut allergy, Arachis hypogaea 2 (Ara h 2) and Arachis hypogaea 6 (Ara h 6) are two clinically relevant peanut allergens with known structural and sequence homology and demonstrated cross-reactivity. We have previously utilized X-ray crystallography and epitope binning to define the epitopes on Ara h 2. We aimed to quantitatively characterize the cross-reactivity between Ara h 2 and Ara h 6 on a molecular level using human monoclonal antibodies (mAbs) and structural characterization of allergenic epitopes. We utilized mAbs cloned from Ara h 2 positive single B cells isolated from peanut-allergic, oral immunotherapy-treated patients to quantitatively analyze cross-reactivity between recombinant Ara h 2 (rAra h 2) and Ara h 6 (rAra h 6) proteins using biolayer interferometry and indirect inhibitory ELISA. Molecular dynamics simulations assessed time-dependent motions and interactions in the antibody-antigen complexes. Three epitopes-conformational epitopes 1.1 and 3, and the sequential epitope KRELRNL/KRELMNL-are conserved between Ara h 2 and Ara h 6, while two more conformational and three sequential epitopes are not. Overall, mAb affinity was significantly lower to rAra h 6 than it was to rAra h 2. This difference in affinity was primarily due to increased dissociation of the antibodies from rAra h 6, a phenomenon explained by the higher conformational flexibility of the Ara h 6-antibody complexes in comparison to Ara h 2-antibody complexes. Our results further elucidate the cross-reactivity of peanut 2S albumins on a molecular level and support the clinical immunodominance of Ara h 2.","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":"25-35"},"PeriodicalIF":3.4,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10929694/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139721849","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}

引用次数: 0

Clinical & Experimental Immunology: Highlights of 2023. 临床与实验免疫学：2023 年亮点。

IF 4.6 3区医学

Clinical and experimental immunology Pub Date : 2024-02-27 DOI: 10.1093/cei/uxae017

Leonie S Taams, Sevda Dogan

引用次数: 0

IAPs and RIPK1 mediate LPS-induced cytokine production in healthy subjects and Crohn's disease. IAPs 和 RIPK1 在健康人和克罗恩病患者中介导 LPS 诱导的细胞因子产生。

IF 3.4 3区医学

Clinical and experimental immunology Pub Date : 2024-02-19 DOI: 10.1093/cei/uxad092

Jakob Benedict Seidelin, Simone Jensen, Morten Hansen, Mariana Rodrigues de Carvalho Bronze, Delphine Cuchet-Lourenҫo, Sergey Nejentsev, Eric Charles LaCasse, Ole Haagen Nielsen

{"title":"IAPs and RIPK1 mediate LPS-induced cytokine production in healthy subjects and Crohn's disease.","authors":"Jakob Benedict Seidelin, Simone Jensen, Morten Hansen, Mariana Rodrigues de Carvalho Bronze, Delphine Cuchet-Lourenҫo, Sergey Nejentsev, Eric Charles LaCasse, Ole Haagen Nielsen","doi":"10.1093/cei/uxad092","DOIUrl":"10.1093/cei/uxad092","url":null,"abstract":"Innate immune activity fuels intestinal inflammation in Crohn's disease (CD), an inflammatory bowel disease. Identification and targeting of new molecular regulators of the innate activity are warranted to control the disease. Inhibitor of apoptosis proteins (IAPs) regulate both cell survival and inflammatory signaling. We investigated the effects of IAP inhibition by second mitochondria-derived activator of caspases (SMAC) mimetics (SMs) on innate responses and cell death to pathogen-associated molecular patterns in peripheral blood mononuclear cells (PBMCs) and monocytes. IAPs inhibited lipopolysaccharide (LPS)-induced expression of proinflammatory interleukin (IL)-1β, IL-6. Likewise, LPS (but not muramyl dipeptide or Escherichia coli) induced TNF-α was inhibited in CD and control PBMCs. The SM effect was partially reversed by inhibition of receptor-interacting serine/threonine-protein kinase 1 (RIPK1). The effect was mainly cell death independent. Thus, IAP inhibition by SMs leads to reduced production of proinflammatory cytokines and may be considered in the efforts to develop new therapeutic strategies to control CD.","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":"291-301"},"PeriodicalIF":3.4,"publicationDate":"2024-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10876114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10381119","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}

引用次数: 0