Zoe Möller-Ramon, Maria Aslani, Nikola Sobczak, Michael Hristov, Christian Weber, Antal Rot, Johan Duchêne
{"title":"The 129 strain-derived passenger mutations in ACKR1-deficient mice alter the expression of PYHIN and Fc-gamma receptor genes.","authors":"Zoe Möller-Ramon, Maria Aslani, Nikola Sobczak, Michael Hristov, Christian Weber, Antal Rot, Johan Duchêne","doi":"10.1093/jleuko/qiae208","DOIUrl":"10.1093/jleuko/qiae208","url":null,"abstract":"<p><p>Most genetically modified mice have been produced using 129 strain-derived embryonic stem cells. Despite ample backcrosses with other strains, these may retain characteristics for 129 passenger mutations, leading to confounding phenotypes unrelated to targeted genes. Here we show that widely used Ackr1-/-129ES mice have approximately 6 Mb of the 129-derived genome retained adjacently to the Ackr1 locus on chromosome 1, including several characteristic polymorphisms. These most notably affect the expression of PYHIN and Fc-gamma receptor genes in myeloid cells, resulting in the overproduction of IL-1β by activated macrophages and the loss of Fc-gamma receptors on myeloid progenitor cells. Therefore, caution is warranted when interpreting Ackr1-/-129ES mouse phenotypes as being solely due to the ACKR1 deficiency. Our findings call for a careful reevaluation of data from previous studies using Ackr1-/-129ES mice and underscore the limitations and pitfalls inherent to mouse models produced using traditional genetic engineering techniques involving 129 embryonic stem cells.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348323","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}
Esmeralda Juárez, Joel A Vázquez-Pérez, Laura E Carreto-Binaghi, Claudia A Martínez-Sanabria, Manuel G Salgado-Cantú, Carmen Sarabia, María Teresa Herrera, Silvia Guzmán-Beltrán, Luis H Gutiérrez-González, Yolanda González
{"title":"COVID-19 extracellular vesicles display heterogeneity based on viral and host RNA expression: implications for host immune response.","authors":"Esmeralda Juárez, Joel A Vázquez-Pérez, Laura E Carreto-Binaghi, Claudia A Martínez-Sanabria, Manuel G Salgado-Cantú, Carmen Sarabia, María Teresa Herrera, Silvia Guzmán-Beltrán, Luis H Gutiérrez-González, Yolanda González","doi":"10.1093/jleuko/qiae212","DOIUrl":"10.1093/jleuko/qiae212","url":null,"abstract":"<p><p>Viral RNA and miRNAs released by immune cells contribute to inflammation in COVID-19 patients. Here, we investigated the role of SARS-CoV2 RNA and host miRNAs carried within extracellular vesicles (EVs) in modulating inflammation. EVs were classified as positive or negative depending on their viral RNA cargo. To assess the function of viral RNA, EVs, and lipopolysaccharide (LPS) were used to stimulate whole blood samples from healthy subjects, and the secretion of 27 serum analytes was measured. EVs alone did not induce cytokines, chemokines, or growth factors. However, under LPS stimulation, (SARS-CoV2+) EVs increased IL-12 and decreased IL-13 secretion, while (SARS-CoV2-) EVs increased MIP-1α and IL-1β secretion. Host miR-19a-3p, -192-5p, -let-7c-5p, and -92b-3a were differentially expressed in association with viral RNA. EVs from COVID-19 patients exhibited differences in viral RNA and miRNA expression profiles that modulate LPS responses. This knowledge sheds light on the immunopathology of COVID-19.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348319","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":"Correction to: EP2/EP4 targeting prevents tumor-derived PGE2-mediated immunosuppression in cDC2s.","authors":"","doi":"10.1093/jleuko/qiae213","DOIUrl":"10.1093/jleuko/qiae213","url":null,"abstract":"","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605092","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}
Amit Kumar, Da'Kuawn Johnson, Alicia Bukowski, Michael J Noto, Nicholas H Carbonetti
{"title":"Interferon lambda signaling in neutrophils enhances the pathogenesis of Bordetella pertussis infection.","authors":"Amit Kumar, Da'Kuawn Johnson, Alicia Bukowski, Michael J Noto, Nicholas H Carbonetti","doi":"10.1093/jleuko/qiae202","DOIUrl":"10.1093/jleuko/qiae202","url":null,"abstract":"<p><p>Interferon lambda plays diverse roles in bacterial infections. Previously, we showed that interferon lambda is induced in the lungs of Bordetella pertussis-infected adult mice and exacerbates inflammation. Here, we report that mice lacking the interferon lambda receptor 1 specifically on neutrophils (MRP8creIFNLR1fl/fl mice) exhibit reduced lung bacterial load and inflammation compared to wild-type mice during B. pertussis infection. In B. pertussis-infected wild-type mice, lung type I and III IFN responses were higher than in MRP8creIFNLR1fl/fl mice, correlating with increased lung inflammatory pathology. There was an increased proportion of interferon gamma-producing neutrophils in the lungs of MRP8creIFNLR1fl/fl mice compared to wild-type mice. IFNLR1-/- neutrophils incubated with B. pertussis exhibited higher killing compared to wild-type neutrophils. Treatment of wild-type neutrophils with interferon lambda further decreased their bacterial killing capacity and treatment of wild-type mice with interferon lambda increased lung bacterial loads. Contributing to the differential killing, we found that IFNLR1-/- neutrophils exhibit higher levels of reactive oxygen species, myeloperoxidase, matrix metalloproteinase-9 activity, neutrophil extracellular traps, and interferon gamma secretion than wild-type neutrophils, and inhibiting NADPH oxidase inhibited bacterial killing in IFNLR1-/- neutrophils. B. pertussis-induced interferon lambda secretion and IFNLR1 gene expression in mouse and human neutrophils and this was dependent on the bacterial virulence protein pertussis toxin. Pertussis toxin enhanced bacterial loads in wild type but not in MRP8creIFNLR1fl/fl or IFNLR1-/- mice. Thus, pertussis toxin disrupts neutrophil function by enhancing type III IFN signaling, which prevents neutrophils from effectively clearing B. pertussis during infection, leading to higher bacterial loads and exacerbation of lung inflammation.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11879762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289243","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":"Receptor tyrosine kinase-like orphan receptor serves as a potential target in cancer immunotherapy.","authors":"Jiaqi Wang, Zhoufang Li, Qi Zhao","doi":"10.1093/jleuko/qiae141","DOIUrl":"10.1093/jleuko/qiae141","url":null,"abstract":"<p><p>Receptor tyrosine kinase-like orphan receptor (ROR), consisting of ROR1 and ROR2, is a conserved family of receptor tyrosine kinase superfamily that plays crucial roles during embryonic development with limited expression in adult normal tissues. However, it is overexpressed in a range of hematological malignancies and solid tumors and functions in cellular processes including cell survival, polarity, and migration, serving as a potential target in cancer immunotherapy. This review summarizes the expression and structure of ROR in developmental morphogenesis and its function in cancers associated with Wnt5a signaling and highlights the cancer immunotherapy strategies targeting ROR.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554968","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}
George B Collins, Jhonatan de Souza Carvalho, Sandali C Jayasinghe, Urte Gumuliauskaite, David M Lowe, David C Thomas, Erik Årstad, Roel P H De Maeyer, Derek W Gilroy
{"title":"A new model measuring bacterial phagocytosis and phagolysosomal oxidation in humans using the intradermal injection of methylene blue-labeled Escherichia coli.","authors":"George B Collins, Jhonatan de Souza Carvalho, Sandali C Jayasinghe, Urte Gumuliauskaite, David M Lowe, David C Thomas, Erik Årstad, Roel P H De Maeyer, Derek W Gilroy","doi":"10.1093/jleuko/qiae217","DOIUrl":"10.1093/jleuko/qiae217","url":null,"abstract":"<p><p>Phagocytosis is an important leukocyte function; however, using existing models it cannot be measured in human tissues in vivo. To address this, we characterized a new phagocytosis model using intradermal methylene blue-labeled Escherichia coli injection (MBEC). Methylene blue (MB) is a licensed human medicine and bacterial stain potentially useful for labeling E. coli that is safe for human injection. Ex vivo coculture of leukocytes with MBEC caused MB to transfer into neutrophils and macrophages by phagocytosis. During this, a \"red shift\" in MB fluorescence was shown to be caused by phagolysosomal oxidation. Hence, MBEC coculture could be used to measure phagocytosis and phagolysosomal oxidation in humans, ex vivo. In healthy volunteers, inflammatory exudate sampling using suction blisters 2 to 24 h after intradermal MBEC injection showed that tissue-acquired neutrophils and monocytes contained more MB than their circulating counterparts, whereas blood and inflamed tissue T, B, and natural killer cells were MBlo. This was validated with spectral flow cytometry by visualizing the MB emission spectrum in tissue-acquired neutrophils. Neutrophil MB emission spectra demonstrated more red shift at 24 h compared with earlier time points, in keeping with progressive phagolysosomal MB oxidation in neutrophils over time in vivo. This new MBEC model can therefore measure bacterial phagocytosis and phagolysosomal oxidation in human skin, in vivo. This has a number of important research applications, e.g. in studying human phagocyte biology, testing novel antimicrobials, and understanding why certain groups such as males, the elderly or those with diabetes, recent surgery, or malnutrition are at increased risk of bacterial infection.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11879004/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142467618","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":"How to focus on autoantigen-specific lymphocytes: a review on diagnosis and treatment of Sjogren's syndrome.","authors":"Bingxia Ming, Ling Li, Shaozhe Cai, Ziwei Hu, Rongfen Gao, Hisanori Umehara, Jixin Zhong, Fang Zheng, Lingli Dong","doi":"10.1093/jleuko/qiae247","DOIUrl":"https://doi.org/10.1093/jleuko/qiae247","url":null,"abstract":"<p><p>Sjogren's syndrome (SS) is an autoimmune epithelitis characterized by focal lymphocytic infiltration against self-antigens leading to progressive glandular dysfunction, which can develop to multisystem manifestation. The classification criteria for SS emphasizes glandular lymphocyte infiltrates and anti-SSA/SSB seropositivity, which is usually manifested in advanced patients. Therapeutically, apart from symptomatic treatment, treatment of SS is based on glucocorticoids and conventional synthetic disease-modifying antirheumatic drugs with global immunosuppression, but the efficacy of biologic or targeted synthetic therapies is still sparse. Currently, emerging studies focus on autoantigen-specific immunotherapies to treat autoimmune disorders by directly eliminating autoreactive cell subsets and inducing tolerance by increasing the autoreactive regulatory lymphocytes. Herein, we summarize the current state of research on the autoantigen-specific approaches for detecting autoreactive lymphocytes and outline the current autoantigen-specific immunotherapies in other autoimmune disorders and their attempts in treatment of SS. Last, we discuss the potential value of focusing on autoantigen-specific lymphocytes in the early diagnosis, monitoring, and targeted treatment of SS. Potential strategies for targeting autoreactive lymphocytes need to be confirmed in SS.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":"117 2","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425597","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":"Six-compound combo remedy ameliorates corticosterone-induced depressive behaviors in mice via targeting 5-hydroxytryptamine receptor 1A signaling.","authors":"Yilu Sun, Qilei Chen, Wei Cui, Hubiao Chen, Jia Zhao, Jianhui Rong","doi":"10.1093/jleuko/qiae167","DOIUrl":"10.1093/jleuko/qiae167","url":null,"abstract":"<p><p>Dysregulation of brain innate immunity involving microglia is implicated in the pathology of neurological disorders including depression. Depression is a prominent medical challenge to global public health systems. Synthetic antidepressant drugs are limited by severe side effects. The present study aimed to identify the active compounds from the well-documented herbal medicine formula Banxia-Houpo decoction (BHD) and discover the underlying mechanisms for tuning microglia. We initially employed Liquid chromatography-mass spectrometry (LC-MS) profiling and network pharmacology analysis to predict the active compound-target interaction networks. We subsequently validated the potential active compounds and targets in a mouse model of corticosterone (CORT)-induced depression and postsynaptic microglia BV2 cells. As a result, 64 compounds were identified in the ethanolic Banxia-Houpo decoction extract and predicted to target 25 depression-related genes. Interestingly, the serotonergic synapse pathway received the highest enrichment score while 5-hydroxytryptamine receptor 1A (HTR1A) was targeted by 6 compounds (i.e. baicalein, luteolin, N-nornuciferine, roemerine, scutellarin, and 6-shogaol). In parallel assays, a six-compound combo (SCC) and Banxia-Houpo decoction markedly ameliorated the depressive-like behaviors in corticosterone-lesioned mice and well-protected highly differentiated (HD) PC12 cells against corticosterone challenge. Moreover, six-compound combo and Banxia-Houpo decoction effectively induced hydroxytryptamine receptor 1A expression in mice and postsynaptic microglia BV2 cells. Hydroxytryptamine receptor 1A antagonist WAY-100635 at 1 mg/kg/d via intraperitoneal injection attenuated the effects of six-compound combo and Banxia-Houpo decoction on the depressive behaviors in mice. These results suggest that six-compound combo might be a potential remedy against depression and other neurological disorders via targeting hydroxytryptamine receptor 1A in microglia.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141855694","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}
Lou Martha Wackerbarth, Sonja Birke Seifert, Matteo Napoli, Ina Rohwedder, Thomas Vogl, Christoph Scheiermann, Thomas Kolben, Claudia Nussbaum, Monika Pruenster, Roland Immler, Markus Sperandio
{"title":"Neonatal neutrophils exhibit reduced NLRP3 inflammasome activation.","authors":"Lou Martha Wackerbarth, Sonja Birke Seifert, Matteo Napoli, Ina Rohwedder, Thomas Vogl, Christoph Scheiermann, Thomas Kolben, Claudia Nussbaum, Monika Pruenster, Roland Immler, Markus Sperandio","doi":"10.1093/jleuko/qiae206","DOIUrl":"10.1093/jleuko/qiae206","url":null,"abstract":"<p><p>Newborns are at high risk to develop sepsis. This is linked to innate immune responses at birth which are not completely adapted to postnatal life. Neutrophils are key players of innate immunity and exhibit a marked ontogenetic regulation of their functionality. Here, we studied the NLRP3 inflammasome in neonatal neutrophils and found lower baseline expression of NLRP3, pro-caspase-1, and the K+-channel KV1.3 compared with adult neutrophils. Following stimulation with lipopolysaccharide/nigericin, apoptosis-related speck-like protein containing a caspase recruitment domain oligomerization, caspase-1 activation, and interleukin-1β (IL-1β) release were significantly reduced in neonatal compared with adult neutrophils. Similarly, stimulation of neonatal neutrophils with E-selectin led to reduced NLRP3 inflammasome activation accompanied by diminished release of the alarmin S100A8/A9. Taken together, our results strongly indicate diminished NLRP3 inflammasome activation in neonatal neutrophils leading to a significant reduction of released IL-1β and S100A8/A9. These findings identify reduced neutrophil NLRP3 inflammasome activation as a critical component contributing to the inherent susceptibility to infections in neonates.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289254","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}
Katrin Becker, Zhaoping Ding, Pascal Bouvain, Jeny Koshy, Timo Massold, Patricia Kleimann, Ulrich Flögel, Sebastian Temme
{"title":"Inflammatory stimuli impact on cellular uptake and biodistribution of perfluorocarbon nanoemulsions.","authors":"Katrin Becker, Zhaoping Ding, Pascal Bouvain, Jeny Koshy, Timo Massold, Patricia Kleimann, Ulrich Flögel, Sebastian Temme","doi":"10.1093/jleuko/qiae199","DOIUrl":"10.1093/jleuko/qiae199","url":null,"abstract":"<p><p>Intravenously administered perfluorocarbon nanoemulsions (PFCs) are taken up by phagocytic immune cells, which enables the noninvasive visualization of inflammatory hot spots by combined 1H/19F magnetic resonance imaging. However, little is known about the influence of inflammatory stimuli on cellular uptake and biodistribution of PFCs. Here, we systematically investigated the impact of inflammation induced by subcutaneous implantation of Matrigel/lipopolysaccharide or myocardial infarction (50 min ischemia reperfusion) on PFC uptake and biodistribution in C57BL/6J mice. We detected strong 19F signals in Matrigel/lipopolysaccharide plugs and infarcted hearts, which were completely absent in controls. Cellular uptake of PFCs was increased in neutrophils isolated from the blood and Matrigel/lipopolysaccharide plugs, whereas uptake by monocytes was only slightly elevated. In contrast, myocardial infarction caused only a moderate early increase of PFC uptake in monocytes and neutrophils. Interestingly, the inflammatory model did also affect the biodistribution of the PFCs. The blood half-life of PFCs was slightly increased after Matrigel/lipopolysaccharide implantation, whereas it was reduced after myocardial infarction. Compared to controls, the 19F signal of the liver was significantly stronger in Matrigel/lipopolysaccharide but not in myocardial infarction animals. Interestingly, stimulation of primary immune cells and RAW264.7 macrophages with lipopolysaccharide had no effect on PFC uptake, whereas C-reactive protein incubation elevated internalization of PFCs at least in RAW264.7 cells. In conclusion, we show that the cellular PFC uptake can differ between individual inflammatory conditions. This is an important aspect that has to be considered for the proper interpretation of 1H/19F magnetic resonance imaging data obtained from inflammatory hot spots.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289253","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}