Science Immunology最新文献_第3页

Macrophage LRRK2 hyperactivity impairs autophagy and induces Paneth cell dysfunction 巨噬细胞 LRRK2 活性亢进会损害自噬作用并诱发潘氏细胞功能障碍

IF 17.6 1区医学

Science Immunology Pub Date : 2024-11-08 DOI: 10.1126/sciimmunol.adi7907

Shengxiang Sun, Miki Hodel, Xiang Wang, Javier De Vicente, Talin Haritunians, Anketse Debebe, Chen-Ting Hung, Changqing Ma, Atika Malique, Hoang N. Nguyen, Maayan Agam, Michael T. Maloney, Marisa S. Goo, Jillian H. Kluss, Richa Mishra, Jennifer Frein, Amanda Foster, Samuel Ballentine, Uday Pandey, Justin Kern, Shaohong Yang, Emebet Mengesha, Iyshwarya Balasubramanian, Annie Arguello, Anthony A. Estrada, Nan Gao, Inga Peter, Dermot P. B. McGovern, Anastasia G. Henry, Thaddeus S. Stappenbeck, Ta-Chiang Liu

{"title":"Macrophage LRRK2 hyperactivity impairs autophagy and induces Paneth cell dysfunction","authors":"Shengxiang Sun, Miki Hodel, Xiang Wang, Javier De Vicente, Talin Haritunians, Anketse Debebe, Chen-Ting Hung, Changqing Ma, Atika Malique, Hoang N. Nguyen, Maayan Agam, Michael T. Maloney, Marisa S. Goo, Jillian H. Kluss, Richa Mishra, Jennifer Frein, Amanda Foster, Samuel Ballentine, Uday Pandey, Justin Kern, Shaohong Yang, Emebet Mengesha, Iyshwarya Balasubramanian, Annie Arguello, Anthony A. Estrada, Nan Gao, Inga Peter, Dermot P. B. McGovern, Anastasia G. Henry, Thaddeus S. Stappenbeck, Ta-Chiang Liu","doi":"10.1126/sciimmunol.adi7907","DOIUrl":"10.1126/sciimmunol.adi7907","url":null,"abstract":"<div ><i>LRRK2</i> polymorphisms (G2019S/N2081D) that increase susceptibility to Parkinson’s disease and Crohn’s disease (CD) lead to LRRK2 kinase hyperactivity and suppress autophagy. This connection suggests that LRRK2 kinase inhibition, a therapeutic strategy being explored for Parkinson’s disease, may also benefit patients with CD. Paneth cell homeostasis is tightly regulated by autophagy, and their dysfunction is a precursor to gut inflammation in CD. Here, we found that patients with CD and mice carrying hyperactive <i>LRRK2</i> polymorphisms developed Paneth cell dysfunction. We also found that LRRK2 kinase can be activated in the context of interactions between genes (genetic autophagy deficiency) and the environment (cigarette smoking). Unexpectedly, lamina propria immune cells were the main intestinal cell types that express LRRK2, instead of Paneth cells as previously suggested. We showed that LRRK2-mediated pro-inflammatory cytokine release from phagocytes impaired Paneth cell function, which was rescued by LRRK2 kinase inhibition through activation of autophagy. Together, these data suggest that LRRK2 kinase inhibitors maintain Paneth cell homeostasis by restoring autophagy and may represent a therapeutic strategy for CD.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"9 101","pages":""},"PeriodicalIF":17.6,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142596856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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Monocytes and their doppelgängers: An immunological crossroads 单核细胞及其二倍体：免疫学的十字路口

IF 17.6 1区医学

Science Immunology Pub Date : 2024-11-01 DOI: 10.1126/sciimmunol.adr6672

Alexander Mildner, Simon Yona

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Kupffer cell reverse migration into the liver sinusoids mitigates neonatal sepsis and meningitis 库普弗细胞逆向迁移到肝窦可减轻新生儿败血症和脑膜炎的病情

IF 17.6 1区医学

Science Immunology Pub Date : 2024-11-01 DOI: 10.1126/sciimmunol.adq9704

Bruna Araujo David, Jawairia Atif, Fernanda Vargas e Silva Castanheira, Tamanna Yasmin, Adrien Guillot, Yeni Ait Ahmed, Moritz Peiseler, Josefien W. Hommes, Lilian Salm, Marie-Anne Brundler, Bas G. J. Surewaard, Wael Elhenawy, Sonya MacParland, Florent Ginhoux, Kathy McCoy, Paul Kubes

{"title":"Kupffer cell reverse migration into the liver sinusoids mitigates neonatal sepsis and meningitis","authors":"Bruna Araujo David, Jawairia Atif, Fernanda Vargas e Silva Castanheira, Tamanna Yasmin, Adrien Guillot, Yeni Ait Ahmed, Moritz Peiseler, Josefien W. Hommes, Lilian Salm, Marie-Anne Brundler, Bas G. J. Surewaard, Wael Elhenawy, Sonya MacParland, Florent Ginhoux, Kathy McCoy, Paul Kubes","doi":"10.1126/sciimmunol.adq9704","DOIUrl":"10.1126/sciimmunol.adq9704","url":null,"abstract":"<div >In adults, liver-resident macrophages, or Kupffer cells (KCs), reside in the sinusoids and sterilize circulating blood by capturing rapidly flowing microbes. We developed quantitative intravital imaging of 1-day-old mice combined with transcriptomics, genetic manipulation, and in vivo infection assays to interrogate increased susceptibility of newborns to bloodstream infections. Whereas 1-day-old KCs were better at catching <i>Escherichia coli</i> in vitro, we uncovered a critical 1-week window postpartum when KCs have limited access to blood and must translocate from liver parenchyma into the sinusoids. KC migration was independent of the microbiome but depended on macrophage migration inhibitory factor, its receptor CD74, and the adhesion molecule CD44. On the basis of our findings, we propose a model of progenitor macrophage seeding of the liver sinusoids via a reverse transmigration process from liver parenchyma. These results also illustrate the importance of developing newborn mouse models to understand newborn immunity and disease.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"9 101","pages":""},"PeriodicalIF":17.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciimmunol.adq9704","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142562161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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CAR-ving away OX40L with engineered Tregs 利用工程化 Tregs 清除 OX40L。

IF 17.6 1区医学

Science Immunology Pub Date : 2024-11-01 DOI: 10.1126/sciimmunol.adu0983

Jonathan S. Maltzman

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The pore-forming apolipoprotein APOL7C drives phagosomal rupture and antigen cross-presentation by dendritic cells 形成孔隙的载脂蛋白 APOL7C 驱动吞噬体破裂和树突状细胞的抗原交叉呈递

IF 17.6 1区医学

Science Immunology Pub Date : 2024-11-01 DOI: 10.1126/sciimmunol.adn2168

Gerone A. Gonzales, Song Huang, Liam Wilkinson, Jenny A. Nguyen, Saif Sikdar, Cécile Piot, Victor Naumenko, Jahanara Rajwani, Cassandra M. Wood, Irene Dinh, Melanie Moore, Eymi Cedeño, Neil McKenna, Maria J. Polyak, Sara Amidian, Vincent Ebacher, Nicole L. Rosin, Matheus B. Carneiro, Bas Surewaard, Nathan C. Peters, Christopher H. Mody, Jeff Biernaskie, Robin M. Yates, Douglas J. Mahoney, Johnathan Canton

{"title":"The pore-forming apolipoprotein APOL7C drives phagosomal rupture and antigen cross-presentation by dendritic cells","authors":"Gerone A. Gonzales, Song Huang, Liam Wilkinson, Jenny A. Nguyen, Saif Sikdar, Cécile Piot, Victor Naumenko, Jahanara Rajwani, Cassandra M. Wood, Irene Dinh, Melanie Moore, Eymi Cedeño, Neil McKenna, Maria J. Polyak, Sara Amidian, Vincent Ebacher, Nicole L. Rosin, Matheus B. Carneiro, Bas Surewaard, Nathan C. Peters, Christopher H. Mody, Jeff Biernaskie, Robin M. Yates, Douglas J. Mahoney, Johnathan Canton","doi":"10.1126/sciimmunol.adn2168","DOIUrl":"10.1126/sciimmunol.adn2168","url":null,"abstract":"<div >Conventional dendritic cells (cDCs) generate protective cytotoxic T lymphocyte (CTL) responses against extracellular pathogens and tumors. This is achieved through a process known as cross-presentation (XP), and, despite its biological importance, the mechanism(s) driving XP remains unclear. Here, we show that a cDC-specific pore-forming protein called apolipoprotein L 7C (APOL7C) is up-regulated in response to innate immune stimuli and is recruited to phagosomes. Association of APOL7C with phagosomes led to phagosomal rupture and escape of engulfed antigens to the cytosol, where they could be processed via the endogenous MHC class I antigen processing pathway. Accordingly, mice deficient in APOL7C did not efficiently prime CD8<sup>+</sup> T cells in response to immunization with bead-bound and cell-associated antigens. Together, our data indicate the presence of dedicated apolipoproteins that mediate the delivery of phagocytosed proteins to the cytosol of activated cDCs to facilitate XP.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"9 101","pages":""},"PeriodicalIF":17.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142562144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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TAM-ing the beast with IL-34 blockade 用 IL-34 阻断 TAM--野兽

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Science Immunology Pub Date : 2024-11-01 DOI: 10.1126/sciimmunol.adu0981

Aron Gyorgypal, Robert M. Anthony

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Orientation-dependent CD45 inhibition with viral and engineered ligands 利用病毒配体和工程配体抑制定向依赖性 CD45

IF 17.6 1区医学

Science Immunology Pub Date : 2024-10-25 DOI: 10.1126/sciimmunol.adp0707

Marta T. Borowska, Liu D. Liu, Nathanael A. Caveney, Kevin M. Jude, Won-Ju Kim, Takeya Masubuchi, Enfu Hui, Robbie G. Majzner, K. Christopher Garcia

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Gastrointestinal germinal center B cell depletion and reduction in IgA+ plasma cells in HIV-1 infection 胃肠道生殖中心 B 细胞耗竭和 HIV-1 感染者 IgA + 浆细胞减少

IF 17.6 1区医学

Science Immunology Pub Date : 2024-10-25 DOI: 10.1126/sciimmunol.ado0090

Francesca Cossarini, Joan Shang, Azra Krek, Zainab Al-Taie, Ruixue Hou, Pablo Canales-Herrerias, Minami Tokuyama, Michael Tankelevich, Adam Tillowitz, Divya Jha, Alexandra E. Livanos, Louise Leyre, Mathieu Uzzan, Gustavo Martinez-Delgado, Matthew D. Taylor, Keshav Sharma, Arno R. Bourgonje, Michael Cruz, Giorgio Ioannou, Travis Dawson, Darwin D''Souza, Seunghee Kim-Schulze, Ahmed Akm, Judith A. Aberg, Benjamin K. Chen, Douglas S. Kwon, Sacha Gnjatic, Alexandros D. Polydorides, Andrea Cerutti, Carmen Argmann, Ivan Vujkovic-Cvijin, Mayte Suarez-Fariñas, Francesca Petralia, Jeremiah J. Faith, Saurabh Mehandru

{"title":"Gastrointestinal germinal center B cell depletion and reduction in IgA+ plasma cells in HIV-1 infection","authors":"Francesca Cossarini, Joan Shang, Azra Krek, Zainab Al-Taie, Ruixue Hou, Pablo Canales-Herrerias, Minami Tokuyama, Michael Tankelevich, Adam Tillowitz, Divya Jha, Alexandra E. Livanos, Louise Leyre, Mathieu Uzzan, Gustavo Martinez-Delgado, Matthew D. Taylor, Keshav Sharma, Arno R. Bourgonje, Michael Cruz, Giorgio Ioannou, Travis Dawson, Darwin D''Souza, Seunghee Kim-Schulze, Ahmed Akm, Judith A. Aberg, Benjamin K. Chen, Douglas S. Kwon, Sacha Gnjatic, Alexandros D. Polydorides, Andrea Cerutti, Carmen Argmann, Ivan Vujkovic-Cvijin, Mayte Suarez-Fariñas, Francesca Petralia, Jeremiah J. Faith, Saurabh Mehandru","doi":"10.1126/sciimmunol.ado0090","DOIUrl":"10.1126/sciimmunol.ado0090","url":null,"abstract":"<div >Gastrointestinal (GI) B cells and plasma cells (PCs) are critical to mucosal homeostasis and the host response to HIV-1 infection. Here, high-resolution mapping of human B cells and PCs sampled from the colon and ileum during both viremic and suppressed HIV-1 infection identified a reduction in germinal center (GC) B cells and follicular dendritic cells (FDCs) during HIV-1 viremia. Immunoglobulin A–positive (IgA<sup>+</sup>) PCs are the major cellular output of intestinal GCs and were significantly reduced during viremic HIV-1 infection. PC-associated transcriptional perturbations, including type I interferon signaling, persisted in antiretroviral therapy (ART)–treated individuals, suggesting ongoing disruption of the intestinal immune milieu during ART. GI humoral immune perturbations were associated with changes in the intestinal microbiome composition and systemic inflammation. These findings highlight a key immune defect in the GI mucosa due to HIV-1 viremia.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"9 100","pages":""},"PeriodicalIF":17.6,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciimmunol.ado0090","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142489635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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Erratum for the Research Article “Initiator cell death event induced by SARS-CoV-2 in the human airway epithelium” by K. Liang et al. 对 K. Liang 等人的研究文章 "SARS-CoV-2 在人气道上皮细胞中诱导的启动子细胞死亡事件 "的勘误

IF 17.6 1区医学

Science Immunology Pub Date : 2024-10-18 DOI: 10.1126/sciimmunol.adt4547

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Erratum for the Research Article “Circulating KLRG1+ long-lived effector memory T cells retain the flexibility to become tissue resident” by E. D. Lucas et al. E. D. Lucas 等人的研究文章 "循环中的 KLRG1+ 长效记忆 T 细胞具有成为组织常驻细胞的灵活性 "的勘误。

IF 17.6 1区医学

Science Immunology Pub Date : 2024-10-18 DOI: 10.1126/sciimmunol.adt4549

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