Journal of Leukocyte Biology最新文献

{"title":"New insights on extramedullary granulopoiesis and neutrophil heterogeneity in the spleen and its importance in disease.","authors":"Rongxia Guo, Xuemei Xie, Qian Ren, Pei Xiong Liew","doi":"10.1093/jleuko/qiae220","DOIUrl":"https://doi.org/10.1093/jleuko/qiae220","url":null,"abstract":"<p><p>Neutrophils are traditionally viewed as uncomplicated exterminators that arrive quickly at sites of infection, kill pathogens, and then expire. However, recent studies employing modern transcriptomics coupled with novel imaging modalities have discovered that neutrophils exhibit significant heterogeneity within organs and have complex functional roles ranging from tissue homeostasis to cancer and chronic pathologies. This has revised the view that neutrophils are simplistic butchers, and there has been a resurgent interest in neutrophils. The spleen was described as a granulopoietic organ more than 4 decades ago, and studies indicate that neutrophils are briefly retained in the spleen before returning to circulation after proliferation. Transcriptomic studies have discovered that splenic neutrophils are heterogeneous and distinct compared with those in blood. This suggests that a unique hematopoietic niche exists in the splenic microenvironment, i.e., capable of programming neutrophils in the spleen. During severe systemic inflammation with an increased need of neutrophils, the spleen can adapt by producing neutrophils through emergency granulopoiesis. In this review, we describe the structure and microanatomy of the spleen and examine how cells within the splenic microenvironment help to regulate splenic granulopoiesis. A focus is placed on exploring the increase in splenic granulopoiesis to meet host needs during infection and inflammation. Emerging technologies such as single-cell RNA sequencing, which provide valuable insight into splenic neutrophil development and heterogeneity, are also discussed. Finally, we examine how tumors subvert this natural pathway in the spleen to generate granulocytic suppressor cells to promote tumor growth.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605145","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":"2024-11-08","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}

{"title":"Macrophage foam cell-derived mediator promotes spontaneous fat lipolysis in atherosclerosis models.","authors":"Dipanjan Banerjee, Debarun Patra, Archana Sinha, Dwaipayan Chakrabarty, Aparup Patra, Raktim Sarmah, Upalabdha Dey, Rajdeep Dutta, Sarada K Bhagabati, Ashis K Mukherjee, Aditya Kumar, Durba Pal, Suman Dasgupta","doi":"10.1093/jleuko/qiae210","DOIUrl":"https://doi.org/10.1093/jleuko/qiae210","url":null,"abstract":"<p><p>Ectopic lipid accumulation in macrophages is responsible for the formation of macrophage foam cells (MFCs) which are involved in the crosstalk with the perivascular adipose tissue (PVAT) of the vascular wall that plays a pivotal role in the progression of atherosclerosis. However, the interrelationship between MFCs and PVAT implementing adipocyte dysfunction during atherosclerosis has not yet been established. We hypothesized that MFC-secreted mediator(s) is causally linked with PVAT dysfunction and the succession of atherosclerosis. To test this hypothesis, MFCs were cocultured with adipocytes, or the conditional media of MFCs (MFC-CM) were exposed to adipocytes and found a significant induction of fat lipolysis in adipocytes. The molecular filtration followed by the high-performance liquid chromatography (HPLC) fractionation and liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) analysis of MFC-CM revealed a novel mediator fetuin-A (FetA) that significantly augments toll-like receptor 4 (TLR4)-dependent fat lipolysis in adipocytes. Mechanistically, MFC-derived FetA markedly increased TLR4-dependent c-Jun N-terminal kinases (JNK)/extracellular signal-regulated kinases (ERK) activation that causes spontaneous fat lipolysis implementing adipocyte dysfunction. Thus, the present study provides the first evidence of MFC-derived FetA that induces adipocyte dysfunction by the stimulation of spontaneous fat lipolysis. Therefore, targeting the crosstalk between MFCs and adipocytes could be a newer approach to counter the progression of atherosclerosis.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605144","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":"Glutamine modulates neutrophil recruitment and effector functions during sterile inflammation.","authors":"Katharina E M Hellenthal, Katharina Thomas, Nadine Ludwig, Anika Cappenberg, Lena Schemmelmann, Tobias Tekath, Andreas Margraf, Sina Mersmann, Katharina Henke, Jan Rossaint, Alexander Zarbock, Wida Amini","doi":"10.1093/jleuko/qiae243","DOIUrl":"https://doi.org/10.1093/jleuko/qiae243","url":null,"abstract":"<p><p>During sterile inflammation, tissue damage induces excessive activation and infiltration of neutrophils into tissues, where they critically contribute to organ dysfunction. Tight regulation of neutrophil migration and their effector functions is crucial to prevent overshooting immune responses. Neutrophils utilize more glutamine, the most abundant free α-amino acid in the human blood, than other leukocytes. However, under inflammatory conditions, the body's requirements exceed its ability to produce sufficient amounts of glutamine. This study investigates the impact of glutamine on neutrophil recruitment and their key effector functions. Glutamine treatment effectively reduced neutrophil activation by modulating β2-integrin activity and chemotaxis in vitro. In a murine in vivo model of sterile inflammation induced by renal ischemia-reperfusion injury, glutamine administration significantly attenuated neutrophil recruitment into injured kidneys. Transcriptomic analysis revealed, glutamine induces transcriptomic reprogramming in murine neutrophils, thus improving mitochondrial functionality and glutathione metabolism. Further, glutamine influenced key neutrophil effector functions, leading to decreased production of reactive oxygen species and formation of neutrophil extracellular traps. Mechanistically, we used a transglutaminase 2 inhibitor to identify transglutaminase 2 as a downstream mediator of glutamine effects on neutrophils. In conclusion, our findings suggest that glutamine diminishes activation and recruitment of neutrophils and thus identify glutamine as a potent means to curb overshooting neutrophil responses during sterile inflammation.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590871","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":"The Influence of Skin Microbial Ecology on γδ T Cell Immune Pathways in Allergic Dermatitis Models in Mice.","authors":"Zonghao You, Xiaoyan Zhang, Sujie Huang, Denghui Chen, Yifan Zhu, Gen Li, Xi Chen","doi":"10.1093/jleuko/qiae244","DOIUrl":"https://doi.org/10.1093/jleuko/qiae244","url":null,"abstract":"<p><p>Atopic dermatitis (AD) is a complex disease influenced by alterations in the skin microbiome and immune dysregulation. Despite the recognized role of these factors, the specific pathways by which distinct microbial populations affect skin immunity remain insufficiently understood. On a molecular level, the pathogenesis of AD involves critical cytokines such as IL-4, IL-17, interferon-γ (IFN-γ), and IL-10, which contribute to the imbalance in T helper (Th) cell responses. Importantly, gamma-delta (γδ) T cells, which produce these cytokines and infiltrate affected epithelial cells in AD, have been underexplored. This study seeks to alleviate AD symptoms in mice by adjusting both peripheral and local immune environments through the transplantation of skin microbiota. By employing 16S rRNA sequencing, we characterized the skin microbiome of the mouse model. Our results demonstrate that microbiota intervention significantly reduces skin thickening and serum IgE levels in DNFB-induced AD mice. Additionally, changes in skin microbiota modulated immune cell dynamics, restoring the Th1/Th2 balance and leading to clinical improvement. These findings highlight the critical role of skin microbiota in shaping immune responses, positioning microbiota-based therapies as a potential treatment for AD.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581401","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":"Role of the basic leucine zipper transcription factor BATF2 in modulating immune responses and inflammation in health and disease.","authors":"Rick van der Geest, Janet S Lee","doi":"10.1093/jleuko/qiae245","DOIUrl":"https://doi.org/10.1093/jleuko/qiae245","url":null,"abstract":"<p><p>Basic leucine zipper transcription factor ATF-like 2 (BATF2) is a transcription factor that is known to exhibit tumor-suppressive activity in cancer cells. Within recent years, however, BATF2 has also emerged as an important transcriptional regulator of the immune system. Through its immunomodulatory function, BATF2 has been implicated in a variety of (patho)physiological processes, including host defense against infection, anti-tumor immunity, and maintenance of tissue inflammatory homeostasis. Below, we discuss recent literature that has provided insight into the role of BATF2 as a transcriptional regulator of immune responses in health and disease, including the cell types that express BATF2, the different diseases in which the immunomodulatory effects of BATF2 have been shown to play a role, and the molecular mechanisms through which BATF2 is thought to exert those effects. In doing so, we highlight that the immunological effects of BATF2 are highly context-dependent, and we point out overlap between the mechanisms of action of BATF2 in infectious disease and non-infectious disease. We also discuss areas of interest for future research, the clinical relevance of better understanding BATF2 function, and potential strategies for therapeutic modulation of BATF2.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590878","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":"Blockade of the CCR3 receptor reduces neutrophil recruitment to the lung during acute inflammation.","authors":"Fatima Lopez-Leal, Tecilli Cabellos-Avelar, Diego A Correa-Becerril, Brenda Juarez-Macias, Rodrigo Cervantes-Diaz, Raul F Reyes-Huerta, Guillermo Juarez-Vega, Daniel Gutierrez-Castaneda, Tannya Karen Castro-Jimenez, Jose Bustos-Arriaga, Jose Luis Maravillas-Montero, Araceli Perez-Lopez","doi":"10.1093/jleuko/qiae203","DOIUrl":"10.1093/jleuko/qiae203","url":null,"abstract":"<p><p>Neutrophils represent one of the host's first lines of defense against invading pathogens. However, an aberrant activation can cause damage to the host. In the case of respiratory infections with viral or bacterial pathogens, one of the most common complications is the development of acute respiratory distress syndrome, in which neutrophil infiltration into the lung is a hallmark. Neutrophils gain expression of chemokine receptors under inflammatory conditions, and their activation can amplify the neutrophil responses. Earlier studies showed that neutrophils recruited to the lung mucosa during bacterial infection upregulate expression of CCR3 and ex vivo stimulation of CCR3 results in an increased neutrophil activation. Therefore, the modulation of effector functions or migration of neutrophils to target sites through chemokine receptors constitutes an opportunity for pharmacological intervention. We aimed to determine whether the blockade of the CCR3 using the specific antagonist SB-328437 reduces neutrophil recruitment and inflammation in the lung in the lipopolysaccharide (LPS)-induced lung injury model and influenza infection in mice. We found that neutrophils acquire CCR3 expression in the lung alveolar space. The intraperitoneal administration of SB-328437 reduced neutrophil recruitment to the lung alveolar space and reduced tissue damage in both the LPS-induced lung injury model and influenza infection. Moreover, treatment with SB-328437 reduced the percentage of neutrophils producing TNFα and neutrophil activation in the alveolar space. Together, these data suggest that CCR3 blockade might be a pharmacological strategy to prevent the aberrant neutrophil activation that results detrimental for the host but preserves sufficient effector response to control the pathogen.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":"1198-1207"},"PeriodicalIF":3.6,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289239","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":"Increased allergic inflammation and decreased lung insulin sensitivity in offspring of obese allergic mothers.","authors":"Christopher Luke Damron, Jeffrey C Bloodworth, Aki Hoji, Jose Casasnovas, Kok Lim Kua, Joan M Cook-Mills","doi":"10.1093/jleuko/qiae135","DOIUrl":"10.1093/jleuko/qiae135","url":null,"abstract":"<p><p>Epidemiological studies demonstrate that maternal obesity and maternal allergy are major risk factors for asthma in offspring. However, the impact of maternal allergy and obesity on offspring lung insulin signaling and allergen responsiveness is not known. To evaluate this, allergic and nonallergic female mice were fed a high-fat diet or low-fat diet from 7 wk before pregnancy until weaning. Neonatal pups were allergen-sensitized and allergen-challenged and then were assessed for obesity, insulin signaling, and allergic inflammation. Compared with pups of nonobese nonallergic mothers, allergen-challenged pups of obese nonallergic mothers, nonobese allergic mothers, and obese allergic mothers had bronchoalveolar lavage (BAL) eosinophilia, with the pups of obese allergic mothers having the highest BAL eosinophilia. These pups also had lower insulin-induced lung AKT phosphorylation, indicating a decrease in lung parenchymal insulin sensitivity. In cross-fostering experiments, allergen-challenged pups exposed to both pre- and postnatal obese allergic mothers had the highest level of BAL eosinophilia. Maternal obesity or allergy increased offspring serum allergen-specific IgE and interleukin-5 that was highest when the mother was both obese and allergic. Also, allergen-challenged pups exposed to both pre- and postnatal obese allergic mothers had the highest level of interleukin-5. In summary, offspring born to obese allergic mothers have decreased lung insulin sensitivity and increased lung allergic inflammation. Interestingly, our data also demonstrate that there is both a pregnancy and postpregnancy aspect of maternal allergy and obesity that enhances allergen responsiveness in offspring.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":"985-994"},"PeriodicalIF":3.6,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11531805/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141331091","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":"Deleterious intestinal inflammation in neonatal mice treated with TLR2/TLR6 agonists.","authors":"Mégane Fernandez, Tiffany Pezier, Stylianos Papadopoulos, Fabrice Laurent, Catherine Werts, Sonia Lacroix-Lamandé","doi":"10.1093/jleuko/qiae140","DOIUrl":"10.1093/jleuko/qiae140","url":null,"abstract":"<p><p>By providing innate immune modulatory stimuli, the early-life immune system can be enhanced to increase resistance to infections. Activation of innate cell surface receptors called pattern recognition receptors by Toll-like receptor (TLR) ligands is one promising approach that can help to control infections as described for listeriosis and cryptosporidiosis. In this study, the effect of TLR2/TLR1 and TLR2/TLR6 agonists was compared when injected into neonatal mice. Surprisingly, the stimulation of TLR2/TLR6 led to the death of the neonatal mice, which was not observed in adult mice. The TLR2/TLR6 agonist administration induced higher systemic and intestinal inflammation in both adult and neonatal mice when compared with TLR2/TLR1 agonist. The mortality of neonatal mice was interferon γ dependent and involved the intestinal production of interleukin-22 and interleukin-17A. This study clearly demonstrates that targeting TLRs as new control strategy of neonatal infections has to be used with caution. Depending on its heterodimeric form, TLR2 stimulation can induce more or less severe adverse effects relying on the age-related immune functions of the host.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":"1142-1156"},"PeriodicalIF":3.6,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141317545","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":"Radiation-induced eCIRP impairs macrophage bacterial phagocytosis.","authors":"Satoshi Yamaga, Atsushi Murao, Mian Zhou, Monowar Aziz, Max Brenner, Ping Wang","doi":"10.1093/jleuko/qiae132","DOIUrl":"10.1093/jleuko/qiae132","url":null,"abstract":"<p><p>Macrophages are essential immune cells for host defense against bacterial pathogens after radiation injury. However, the role of macrophage phagocytosis in infection following radiation injury remains poorly examined. Extracellular cold-inducible RNA-binding protein is a damage-associated molecular pattern that dysregulates host immune system responses such as phagocytosis. We hypothesized that radiation-induced extracellular cold-inducible RNA-binding protein release impairs macrophage phagocytosis of bacteria. Adult healthy mice were exposed to 6.5 Gy total body irradiation. Primary peritoneal macrophages isolated from adult healthy mice were exposed to 6.5 Gy radiation. Extracellular cold-inducible RNA-binding protein-neutralizing monoclonal antibody was added to the cell culture prior to irradiation. Bacterial phagocytosis by peritoneal macrophages was assessed using pHrodo Green-labeled Escherichia coli 7 d after irradiation ex vivo and in vitro. Bacterial phagocytosis was also assessed after treatment with recombinant murine cold-inducible RNA-binding protein. Rac1 and ARP2 protein expression in cell lysates and extracellular cold-inducible RNA-binding protein levels in the peritoneal lavage were assessed by western blotting. Bacterial phagocytosis by peritoneal macrophages was significantly decreased after irradiation compared with controls ex vivo and in vitro. Rac1 and ARP2 expression in the peritoneal macrophages were downregulated after total body irradiation. Total body irradiation significantly increased extracellular cold-inducible RNA-binding protein levels in the peritoneal cavity. Recombinant murine cold-inducible RNA-binding protein significantly decreased bacterial phagocytosis in a dose-dependent manner. Extracellular cold-inducible RNA-binding protein monoclonal antibody restored bacterial phagocytosis by peritoneal macrophages after irradiation. Ionizing radiation exposure impairs bacterial phagocytosis by macrophages after irradiation. Neutralization of extracellular cold-inducible RNA-binding protein restores the phagocytic ability of macrophages after irradiation. Our findings elucidate a novel mechanism of immune dysfunction and provide a potential new therapeutic approach for limiting infection after radiation injury.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":"1072-1079"},"PeriodicalIF":3.6,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11531804/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141450691","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}