Eosinophils exhibit a unique transcriptional signature and increased sensitivity to IL-3-induced activation in response to colorectal cancer cells
J Leukoc Biol. 2024 Mar 13:qiae063. doi: 10.1093/jleuko/qiae063. Online ahead of print.ABSTRACTEosinophils have been mainly studied in allergic diseases and parasitic infections. Nonetheless, eosinophils accumulate in a variety of solid tumors, including colorectal cancer, where their presence is associated with improved prognosis. Eosinophils can promote anti-tumor immunity through various mechanisms, including direct cytotoxicity towards tumor cells and promoting T cell activation. However, the mechanisms by which tumor cells regulate eosinophil activities are largely unknown. Herein, we characterized the potential inter...
Source: Journal of Leukocyte Biology - March 13, 2024 Category: Hematology Authors: Michal Itan Shai Dulberg Ayelet Kaminitz Ariel Munitz Asaf Madi Source Type: research

PGAM1 suppression remodels the tumor microenvironment in triple-negative breast cancer and synergizes with anti-PD-1 immunotherapy
In this study, we aimed to investigate the role of PGAM1 in TNBC and determine the potential of PGAM1 inhibition in combination with anti-PD-1 immunotherapy. Our results showed that PGAM1 is highly expressed in TNBC and is associated with poor prognosis. In vivo experiments demonstrated that PGAM1 inhibition synergizes with anti-PD-1 immunotherapy, significantly remodeling the TME and leading to an increase in anti-tumor immunocytes, such as CD8+ T cells and M1-macrophages, and a reduction in immunosuppressive cell infiltration, including myeloid-derived suppressor cells, M2-macrophage, and Tregs. Functional and animal exp...
Source: Journal of Leukocyte Biology - March 13, 2024 Category: Hematology Authors: Dong Zhang Min Wang Wenying Wang Shiya Ma Wenwen Yu Xiubao Ren Qian Sun Source Type: research

IL-4 within the bone marrow: a key driver of lung tumorigenesis
J Leukoc Biol. 2024 Mar 12:qiae033. doi: 10.1093/jleuko/qiae033. Online ahead of print.NO ABSTRACTPMID:38470834 | DOI:10.1093/jleuko/qiae033 (Source: Journal of Leukocyte Biology)
Source: Journal of Leukocyte Biology - March 12, 2024 Category: Hematology Authors: Yoshimasa Tanaka Source Type: research

Administration of a Bacterial Lysate to the Airway Compartment Is Sufficient to Inhibit Allergen-Induced Lung Eosinophilia in Germ-free Mice
J Leukoc Biol. 2024 Mar 12:qiae047. doi: 10.1093/jleuko/qiae047. Online ahead of print.ABSTRACTThe nexus between eosinophils and microbes is attracting increasing attention. We previously showed that airway administration of sterile microbial products contained in dust collected from traditional dairy farms virtually abrogated broncho-alveolar lavage (BAL) eosinophilia and other cardinal asthma phenotypes in allergen-sensitized specific pathogen-free (SPF) mice. Interestingly, comparable inhibition of allergen-induced BAL eosinophilia and promotion of airway barrier integrity were found upon administration of a sterile, ph...
Source: Journal of Leukocyte Biology - March 12, 2024 Category: Hematology Authors: Ashley N Michael Oksana Pivniouk Peace C Ezeh Sunil Banskar Seongmin Hahn Avery DeVries Kathryn O'Connell Vadim Pivniouk Donata Vercelli Source Type: research

IL-4 within the bone marrow: a key driver of lung tumorigenesis
J Leukoc Biol. 2024 Mar 12:qiae033. doi: 10.1093/jleuko/qiae033. Online ahead of print.NO ABSTRACTPMID:38470834 | DOI:10.1093/jleuko/qiae033 (Source: Journal of Leukocyte Biology)
Source: Journal of Leukocyte Biology - March 12, 2024 Category: Hematology Authors: Yoshimasa Tanaka Source Type: research

Administration of a Bacterial Lysate to the Airway Compartment Is Sufficient to Inhibit Allergen-Induced Lung Eosinophilia in Germ-free Mice
J Leukoc Biol. 2024 Mar 12:qiae047. doi: 10.1093/jleuko/qiae047. Online ahead of print.ABSTRACTThe nexus between eosinophils and microbes is attracting increasing attention. We previously showed that airway administration of sterile microbial products contained in dust collected from traditional dairy farms virtually abrogated broncho-alveolar lavage (BAL) eosinophilia and other cardinal asthma phenotypes in allergen-sensitized specific pathogen-free (SPF) mice. Interestingly, comparable inhibition of allergen-induced BAL eosinophilia and promotion of airway barrier integrity were found upon administration of a sterile, ph...
Source: Journal of Leukocyte Biology - March 12, 2024 Category: Hematology Authors: Ashley N Michael Oksana Pivniouk Peace C Ezeh Sunil Banskar Seongmin Hahn Avery DeVries Kathryn O'Connell Vadim Pivniouk Donata Vercelli Source Type: research

Optimization of a lipid nanoparticle-based protocol for RNA transfection into primary mononuclear phagocytes
J Leukoc Biol. 2024 Mar 11:qiae059. doi: 10.1093/jleuko/qiae059. Online ahead of print.ABSTRACTThe effective delivery of synthetic RNA into mononuclear phagocytes is a prerequisite for experimental research and therapeutic development. However, traditional methods are highly ineffective and toxic for these cells. Here, we aimed to optimize a transfection protocol for primary bone marrow-derived phagocytes, specifically dendritic cells and macrophages, using lipid nanoparticles generated by microfluidics. Our results show that a lipid mixture similar to that used in Moderna's COVID-19 mRNA vaccine outperforms the others tes...
Source: Journal of Leukocyte Biology - March 11, 2024 Category: Hematology Authors: Yu Zhang Louis-Charles B éland Sabrina Roussel Nicolas Bertrand S ébastien S Hébert Luc Valli ères Source Type: research

The ecto-enzyme CD38 modulates CD4 T cell immunometabolic responses and participates in HIV pathogenesis
J Leukoc Biol. 2024 Mar 11:qiae060. doi: 10.1093/jleuko/qiae060. Online ahead of print.ABSTRACTDespite abundant evidence correlating T cell CD38 expression and HIV infection pathogenesis, its role as a CD4 T cell immunometabolic regulator remains unclear. We find that CD38's extracellular glycohydrolase activity restricts metabolic reprogramming after TCR-engaging stimulation in Jurkat T CD4 cells, together with functional responses, while reducing intracellular NAD and NMN concentrations. Selective elimination of CD38's ectoenzyme function licenses them to decrease the OCR/ECAR ratio upon TCR signaling and to increase cyc...
Source: Journal of Leukocyte Biology - March 11, 2024 Category: Hematology Authors: Fernando D íaz-Basilio Mois és Vergara-Mendoza Jessica Romero-Rodr íguez Sharik Hern ández-Rizo Alejandro Escobedo-Calvario Luis-Le ón Fuentes-Romero Santiago P érez-Patrigeon Akio Murakami-Ogasawara Mar ía Gomez-Palacio Gustavo Reyes-Ter án Wei J Source Type: research

Eosinophil activation during immune responses: an ultrastructural view with an emphasis on viral diseases
J Leukoc Biol. 2024 Mar 11:qiae058. doi: 10.1093/jleuko/qiae058. Online ahead of print.ABSTRACTEosinophils are cells of the innate immune system that orchestrate complex inflammatory responses. The study of the cell biology of eosinophils, particularly associated with cell activation, is of great interest to understand their immune responses. From a morphological perspective, activated eosinophils show ultrastructural signatures that have provided critical insights into the comprehension of their functional capabilities. Application of conventional transmission electron microscopy (TEM) in combination with quantitative ass...
Source: Journal of Leukocyte Biology - March 11, 2024 Category: Hematology Authors: Rossana C N Melo Thiago P Silva Source Type: research

Optimization of a lipid nanoparticle-based protocol for RNA transfection into primary mononuclear phagocytes
J Leukoc Biol. 2024 Mar 11:qiae059. doi: 10.1093/jleuko/qiae059. Online ahead of print.ABSTRACTThe effective delivery of synthetic RNA into mononuclear phagocytes is a prerequisite for experimental research and therapeutic development. However, traditional methods are highly ineffective and toxic for these cells. Here, we aimed to optimize a transfection protocol for primary bone marrow-derived phagocytes, specifically dendritic cells and macrophages, using lipid nanoparticles generated by microfluidics. Our results show that a lipid mixture similar to that used in Moderna's COVID-19 mRNA vaccine outperforms the others tes...
Source: Journal of Leukocyte Biology - March 11, 2024 Category: Hematology Authors: Yu Zhang Louis-Charles B éland Sabrina Roussel Nicolas Bertrand S ébastien S Hébert Luc Valli ères Source Type: research

The ecto-enzyme CD38 modulates CD4 T cell immunometabolic responses and participates in HIV pathogenesis
J Leukoc Biol. 2024 Mar 11:qiae060. doi: 10.1093/jleuko/qiae060. Online ahead of print.ABSTRACTDespite abundant evidence correlating T cell CD38 expression and HIV infection pathogenesis, its role as a CD4 T cell immunometabolic regulator remains unclear. We find that CD38's extracellular glycohydrolase activity restricts metabolic reprogramming after TCR-engaging stimulation in Jurkat T CD4 cells, together with functional responses, while reducing intracellular NAD and NMN concentrations. Selective elimination of CD38's ectoenzyme function licenses them to decrease the OCR/ECAR ratio upon TCR signaling and to increase cyc...
Source: Journal of Leukocyte Biology - March 11, 2024 Category: Hematology Authors: Fernando D íaz-Basilio Mois és Vergara-Mendoza Jessica Romero-Rodr íguez Sharik Hern ández-Rizo Alejandro Escobedo-Calvario Luis-Le ón Fuentes-Romero Santiago P érez-Patrigeon Akio Murakami-Ogasawara Mar ía Gomez-Palacio Gustavo Reyes-Ter án Wei J Source Type: research

Eosinophil activation during immune responses: an ultrastructural view with an emphasis on viral diseases
J Leukoc Biol. 2024 Mar 11:qiae058. doi: 10.1093/jleuko/qiae058. Online ahead of print.ABSTRACTEosinophils are cells of the innate immune system that orchestrate complex inflammatory responses. The study of the cell biology of eosinophils, particularly associated with cell activation, is of great interest to understand their immune responses. From a morphological perspective, activated eosinophils show ultrastructural signatures that have provided critical insights into the comprehension of their functional capabilities. Application of conventional transmission electron microscopy (TEM) in combination with quantitative ass...
Source: Journal of Leukocyte Biology - March 11, 2024 Category: Hematology Authors: Rossana C N Melo Thiago P Silva Source Type: research

Euphohelioscopin A enhances NK cell antitumor immunity through GSDME-triggered pyroptosis
In this study, various assays were conducted, including NK cell cytotoxicity assays, flow cytometry, xenograft tumor models, real-time PCR, and ELISA to assess NK cell-mediated cell killing, as well as gene and protein expressions. The results indicated that Euphohelioscopin A (Eupho-A), a potential pyroptosis activator, enhances NK cell-mediated lysis of tumor cells, resulting in inhibiting tumor growth that could be reversed by NK cell depletion. Furthermore, we found that Eupho-A significantly enhanced IFN-γ production in NK cells and synergistically up-regulated GSDME with IFN-γ in cancer cells. Eupho-A also increase...
Source: Journal of Leukocyte Biology - March 8, 2024 Category: Hematology Authors: Chenyuan Gong Hongyan Mu Jiaojiao Luo Rujun Zhang Dan Hu Zhenhua Chen Cheng Fang Zhongxian Chen Xinxue Zhu Chao Yao Lixin Wang Yufu Zhou Weimin Zhao Shiguo Zhu Source Type: research

Biologic Therapy in Rare Eosinophil-Associated Disorders: Remaining Questions and Translational Research Opportunities
J Leukoc Biol. 2024 Mar 8:qiae051. doi: 10.1093/jleuko/qiae051. Online ahead of print.ABSTRACTRare eosinophil-associated disorders (EADs), including hypereosinophilic syndrome, eosinophilic granulomatosis with polyangiitis and eosinophilic gastrointestinal disorders, are a heterogeneous group of conditions characterized by blood and/or tissue hypereosinophilia and eosinophil-related clinical manifestations. Although the recent availability of biologic therapies that directly and indirectly target eosinophils has the potential to dramatically improve treatment options for all EADs, clinical trials addressing their safety an...
Source: Journal of Leukocyte Biology - March 8, 2024 Category: Hematology Authors: Paneez Khoury Florence Roufosse Fei Li Kuang Steven J Ackerman Praveen Akuthota Bruce S Bochner Mats W Johansson Sameer K Mathur Princess U Ogbogu Lisa A Spencer Michael E Wechsler Nives Zimmermann Amy D Klion International Eosinophil Society Clinical Res Source Type: research

Euphohelioscopin A enhances NK cell antitumor immunity through GSDME-triggered pyroptosis
In this study, various assays were conducted, including NK cell cytotoxicity assays, flow cytometry, xenograft tumor models, real-time PCR, and ELISA to assess NK cell-mediated cell killing, as well as gene and protein expressions. The results indicated that Euphohelioscopin A (Eupho-A), a potential pyroptosis activator, enhances NK cell-mediated lysis of tumor cells, resulting in inhibiting tumor growth that could be reversed by NK cell depletion. Furthermore, we found that Eupho-A significantly enhanced IFN-γ production in NK cells and synergistically up-regulated GSDME with IFN-γ in cancer cells. Eupho-A also increase...
Source: Journal of Leukocyte Biology - March 8, 2024 Category: Hematology Authors: Chenyuan Gong Hongyan Mu Jiaojiao Luo Rujun Zhang Dan Hu Zhenhua Chen Cheng Fang Zhongxian Chen Xinxue Zhu Chao Yao Lixin Wang Yufu Zhou Weimin Zhao Shiguo Zhu Source Type: research