Pub Date : 2026-02-10DOI: 10.1016/j.immuni.2026.01.021
Juan Zhang, Qiang Liu
Immunotherapeutic approaches to brain aging remain largely preclinical and in early translational stages, and they have focused mostly on modulating innate immunity. In this issue of Immunity, Negredo et al. identify T cells bearing exhaustion-like signatures as a hallmark of brain aging and reveal the beneficial effects of an engineered IL-10 variant that functionally uncouples pro- and anti-inflammatory signaling in microglia.
{"title":"Shedding light on interventions for brain aging","authors":"Juan Zhang, Qiang Liu","doi":"10.1016/j.immuni.2026.01.021","DOIUrl":"https://doi.org/10.1016/j.immuni.2026.01.021","url":null,"abstract":"Immunotherapeutic approaches to brain aging remain largely preclinical and in early translational stages, and they have focused mostly on modulating innate immunity. In this issue of <em>Immunity</em>, Negredo et al. identify T cells bearing exhaustion-like signatures as a hallmark of brain aging and reveal the beneficial effects of an engineered IL-10 variant that functionally uncouples pro- and anti-inflammatory signaling in microglia.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"57 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146145961","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}
Pub Date : 2026-02-09DOI: 10.1016/j.immuni.2025.12.011
Jeffrey Downey, Ana Oliveira-Coelho, Máté G. Kiss, Gabriel Laghlali, Alexander Leunig, Emir Radkevich, Laszlo Halasz, Martin Umali, Joana Ferreira da Silva, Madeline L. Eller, Matteo Gianeselli, Magdalena M. Żak, Haley E. Randolph, Gabriel Caumartin, Wolfram C. Poller, Henrike Janssen, Laura L. Koekkoek, Jamshid Abdul-Ghafar, Pacific Huynh, Darwin D’Souza, Vladimir Roudko, Sheqouia Nauta, Jazz Munitz, Xisheng Li, Thomas Rathner, Ziche Chen, Anh Phan, Abigail Glick, Katarzyna Cialowicz, Zhihong Chen, Seunghee Kim-Schulze, Seonghun Yoon, Matthias Nahrendorf, Susmita Sahoo, Miriam Merad, Adolfo García-Sastre, Cameron S. McAlpine, Gustav J. Strijkers, Viviana Simon, Rachel Brody, Saurabh Mehandru, Zahi A. Fayad, Benjamin P. Kleinstiver, Lior Zangi, Mandy M.T. van Leent, Michael Schotsaert, Filip K. Swirski
Abundant evidence has correlated influenza infection with cardiovascular disease, yet mechanisms linking infection with the heart remain poorly understood. Here, we show that influenza infection damaged the human and murine heart. In mice, we showed that shortly after pulmonary infection, the virus infected a circulating myeloid pro-dendritic cell 3 (pro-DC3) that expressed high concentrations of the chemokine receptor CCR2. The heart, which produces abundant CCL2, preferentially attracted infected pro-DC3. In the myocardium, the virus escaped pro-DC3, infected cardiomyocytes, and triggered production of type-I interferon (IFN-I). Engagement of the IFN-I receptor (IFNAR1) on cardiomyocytes caused tissue damage and compromised heart function. Genetically and therapeutically dampening IFNAR1 exclusively in cardiomyocytes protected the heart while preserving anti-viral immunity in the lung. Our results identify a series of host-pathogen interactions that propagate tissue damage and uncover an axis for intervention to mitigate cardiovascular risk following viral infection.
{"title":"Influenza hijacks myeloid cells to inflict type-I interferon-fueled damage in the heart","authors":"Jeffrey Downey, Ana Oliveira-Coelho, Máté G. Kiss, Gabriel Laghlali, Alexander Leunig, Emir Radkevich, Laszlo Halasz, Martin Umali, Joana Ferreira da Silva, Madeline L. Eller, Matteo Gianeselli, Magdalena M. Żak, Haley E. Randolph, Gabriel Caumartin, Wolfram C. Poller, Henrike Janssen, Laura L. Koekkoek, Jamshid Abdul-Ghafar, Pacific Huynh, Darwin D’Souza, Vladimir Roudko, Sheqouia Nauta, Jazz Munitz, Xisheng Li, Thomas Rathner, Ziche Chen, Anh Phan, Abigail Glick, Katarzyna Cialowicz, Zhihong Chen, Seunghee Kim-Schulze, Seonghun Yoon, Matthias Nahrendorf, Susmita Sahoo, Miriam Merad, Adolfo García-Sastre, Cameron S. McAlpine, Gustav J. Strijkers, Viviana Simon, Rachel Brody, Saurabh Mehandru, Zahi A. Fayad, Benjamin P. Kleinstiver, Lior Zangi, Mandy M.T. van Leent, Michael Schotsaert, Filip K. Swirski","doi":"10.1016/j.immuni.2025.12.011","DOIUrl":"https://doi.org/10.1016/j.immuni.2025.12.011","url":null,"abstract":"Abundant evidence has correlated influenza infection with cardiovascular disease, yet mechanisms linking infection with the heart remain poorly understood. Here, we show that influenza infection damaged the human and murine heart. In mice, we showed that shortly after pulmonary infection, the virus infected a circulating myeloid pro-dendritic cell 3 (pro-DC3) that expressed high concentrations of the chemokine receptor CCR2. The heart, which produces abundant CCL2, preferentially attracted infected pro-DC3. In the myocardium, the virus escaped pro-DC3, infected cardiomyocytes, and triggered production of type-I interferon (IFN-I). Engagement of the IFN-I receptor (IFNAR1) on cardiomyocytes caused tissue damage and compromised heart function. Genetically and therapeutically dampening IFNAR1 exclusively in cardiomyocytes protected the heart while preserving anti-viral immunity in the lung. Our results identify a series of host-pathogen interactions that propagate tissue damage and uncover an axis for intervention to mitigate cardiovascular risk following viral infection.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"315 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146146750","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}
Pub Date : 2026-01-30DOI: 10.1016/j.immuni.2026.01.013
Dianyu Chen, Heping Xu
The meninges, long viewed as passive protective membranes, are now recognized as active immunological interfaces harboring diverse immune populations. Among them, B cells have emerged as dynamic participants in central nervous system (CNS) homeostasis and disorders. Recent studies have identified distinct B cell subsets in the meninges at different developmental and activation stages, including precursors supported by skull marrow-derived progenitors and immunoglobulin A (IgA)⁺ plasma cells influenced by gut microbiota. These meningeal B cells contribute to immune tolerance, barrier protection, and potentially neural development and repair, while also exhibiting context-dependent pathogenic roles in CNS autoimmunity, aging, and neurodegeneration. In this review, we discuss the current knowledge of meningeal B cells and highlight key future research directions aimed at understanding their cellular dynamics, activation and differentiation processes, and the balance between protective and deleterious functions.
{"title":"Meningeal B cells: Emerging players at the brain border","authors":"Dianyu Chen, Heping Xu","doi":"10.1016/j.immuni.2026.01.013","DOIUrl":"https://doi.org/10.1016/j.immuni.2026.01.013","url":null,"abstract":"The meninges, long viewed as passive protective membranes, are now recognized as active immunological interfaces harboring diverse immune populations. Among them, B cells have emerged as dynamic participants in central nervous system (CNS) homeostasis and disorders. Recent studies have identified distinct B cell subsets in the meninges at different developmental and activation stages, including precursors supported by skull marrow-derived progenitors and immunoglobulin A (IgA)⁺ plasma cells influenced by gut microbiota. These meningeal B cells contribute to immune tolerance, barrier protection, and potentially neural development and repair, while also exhibiting context-dependent pathogenic roles in CNS autoimmunity, aging, and neurodegeneration. In this review, we discuss the current knowledge of meningeal B cells and highlight key future research directions aimed at understanding their cellular dynamics, activation and differentiation processes, and the balance between protective and deleterious functions.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"14 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146089433","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}
Pub Date : 2026-01-30DOI: 10.1016/j.immuni.2025.12.013
Katharina Daniel, Leon Ullrich, Denis Ruchnewitz, Matthijs Meijers, Nico Joel Halwe, Ursula Wild, Jan Eberhardt, Jacob Schön, Ricarda Stumpf, Maike Schlotz, Marie Wunsch, Luana Girao Lessa, Elsayed Mohammed Abdelwhab, Maryna Kuryshko, Christopher Dietrich, Andreas Pinger, Anna-Lena Schumacher, Maximilian Germer, Malena Rohde, Christian Kukat, Lutz Gieselmann, Henning Gruell, Donata Hoffmann, Martin Beer, Thomas Erren, Michael Lässig, Christoph Kreer, Florian Klein
{"title":"Pre-existing neutralizing antibodies against cattle-transmitted influenza A virus H5N1 are detectable in unexposed individuals","authors":"Katharina Daniel, Leon Ullrich, Denis Ruchnewitz, Matthijs Meijers, Nico Joel Halwe, Ursula Wild, Jan Eberhardt, Jacob Schön, Ricarda Stumpf, Maike Schlotz, Marie Wunsch, Luana Girao Lessa, Elsayed Mohammed Abdelwhab, Maryna Kuryshko, Christopher Dietrich, Andreas Pinger, Anna-Lena Schumacher, Maximilian Germer, Malena Rohde, Christian Kukat, Lutz Gieselmann, Henning Gruell, Donata Hoffmann, Martin Beer, Thomas Erren, Michael Lässig, Christoph Kreer, Florian Klein","doi":"10.1016/j.immuni.2025.12.013","DOIUrl":"https://doi.org/10.1016/j.immuni.2025.12.013","url":null,"abstract":"","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"29 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146089431","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}
Pub Date : 2026-01-30DOI: 10.1016/j.immuni.2026.01.004
Simon Grassmann, Endi K. Santosa, Hyunu Kim, Isabelle B. Johnson, Adriana M. Mujal, Jean-Benoit LeLuduec, Sherry X. Fan, Mark Owyong, Adrian Straub, Liang Deng, Katharine C. Hsu, Dirk H. Busch, Colleen M. Lau, Joseph C. Sun
{"title":"Stepwise epigenetic signal integration drives adaptive programming of cytotoxic lymphocytes","authors":"Simon Grassmann, Endi K. Santosa, Hyunu Kim, Isabelle B. Johnson, Adriana M. Mujal, Jean-Benoit LeLuduec, Sherry X. Fan, Mark Owyong, Adrian Straub, Liang Deng, Katharine C. Hsu, Dirk H. Busch, Colleen M. Lau, Joseph C. Sun","doi":"10.1016/j.immuni.2026.01.004","DOIUrl":"https://doi.org/10.1016/j.immuni.2026.01.004","url":null,"abstract":"","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"30 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146089432","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}
Pub Date : 2026-01-30DOI: 10.1016/j.immuni.2026.01.016
Paloma Navarro Negredo, Justin You, Max Hauptschein, Adam B. Schroer, Daniel J. Richard, Gita C. Abhiraman, Andy P. Tsai, Eric D. Sun, Giulia Notarangelo, Julliana Ramirez-Matias, Olivia Y. Zhou, Matthew T. Buckley, Karen E. Malacon, Lucy Xu, Juliana Sucharov, Eduardo Ramirez Lopez, Lora Picton, Tony Wyss-Coray, Robert A. Saxton, Ricardo A. Fernandes, Saul A. Villeda, K. Christopher Garcia, Anne Brunet
The immune system could play an important role in the age-related decline in brain function, yet specific immune-based strategies to enhance brain resilience in older individuals are lacking. Here, we combined engineered proteins and direct brain delivery to target immune cell populations within the old brain. We detected T cells with an exhaustion signature in the old brain and targeted them with a potent engineered checkpoint inhibitor (RIPR-PD1). This led to T cell expansion and strong pro-inflammatory responses in many brain cell types, notably microglia. To rescue age-related inflammatory imbalances in microglia, we used the anti-inflammatory cytokine interleukin (IL)-10. IL-10 boosted anti-inflammatory responses in old microglia, but it also triggered pro-inflammatory signaling. An engineered IL-10 variant that uncouples pro- and anti-inflammatory responses positively impacted the transcriptome of multiple cell types, enhanced neurogenesis, and improved cognition in aged mice. Our findings pave the way for immunotherapies for the aged brain.
{"title":"Targeting immune cells in the aged brain reveals that engineered cytokine IL-10 enhances neurogenesis and improves cognition","authors":"Paloma Navarro Negredo, Justin You, Max Hauptschein, Adam B. Schroer, Daniel J. Richard, Gita C. Abhiraman, Andy P. Tsai, Eric D. Sun, Giulia Notarangelo, Julliana Ramirez-Matias, Olivia Y. Zhou, Matthew T. Buckley, Karen E. Malacon, Lucy Xu, Juliana Sucharov, Eduardo Ramirez Lopez, Lora Picton, Tony Wyss-Coray, Robert A. Saxton, Ricardo A. Fernandes, Saul A. Villeda, K. Christopher Garcia, Anne Brunet","doi":"10.1016/j.immuni.2026.01.016","DOIUrl":"https://doi.org/10.1016/j.immuni.2026.01.016","url":null,"abstract":"The immune system could play an important role in the age-related decline in brain function, yet specific immune-based strategies to enhance brain resilience in older individuals are lacking. Here, we combined engineered proteins and direct brain delivery to target immune cell populations within the old brain. We detected T cells with an exhaustion signature in the old brain and targeted them with a potent engineered checkpoint inhibitor (RIPR-PD1). This led to T cell expansion and strong pro-inflammatory responses in many brain cell types, notably microglia. To rescue age-related inflammatory imbalances in microglia, we used the anti-inflammatory cytokine interleukin (IL)-10. IL-10 boosted anti-inflammatory responses in old microglia, but it also triggered pro-inflammatory signaling. An engineered IL-10 variant that uncouples pro- and anti-inflammatory responses positively impacted the transcriptome of multiple cell types, enhanced neurogenesis, and improved cognition in aged mice. Our findings pave the way for immunotherapies for the aged brain.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"180 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146089434","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}
Pub Date : 2026-01-30DOI: 10.1016/j.immuni.2026.01.015
Juliette Gauthier, Maxime Maugendre, Simon Léonard, Yoni Desvois, Maïwenn Pineau, Romain Pinon, Nicolas Hipp, Karin Tarte, Patricia Amé, Sophie Hillion, Laure Michel, Céline Delaloy
{"title":"B cell-intrinsic IL-2 signaling regulates inflammation by promoting IL-10 expression in CD25+ age-associated B cells","authors":"Juliette Gauthier, Maxime Maugendre, Simon Léonard, Yoni Desvois, Maïwenn Pineau, Romain Pinon, Nicolas Hipp, Karin Tarte, Patricia Amé, Sophie Hillion, Laure Michel, Céline Delaloy","doi":"10.1016/j.immuni.2026.01.015","DOIUrl":"https://doi.org/10.1016/j.immuni.2026.01.015","url":null,"abstract":"","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"56 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146089435","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}
Pub Date : 2026-01-29DOI: 10.1016/j.immuni.2026.01.005
Miqdad O. Dhariwala, Ricardo O. Carale, Andrea M. DeRogatis, Henry Rodriguez-Valbuena, Joy N. Okoro, Christina A. Ekstrand, Antonin Weckel, Victoria M. Tran, Irek Habrylo, Rio Barrere-Cain, Oluwasunmisola T. Ojewumi, Allison E. Tammen, Jessica Tsui, Saba Shaikh, Shivaram Yellamilli, Ahmed K. Aladhami, Robin Schwartz, John M. Leech, Geil R. Merana, Kamir J. Hiam-Galvez, Matthias Mack, Joanna Halkias, James M. Gardner, Rachel L. Rutishauser, Gabriela K. Fragiadakis, Matthew H. Spitzer, Alexis J. Combes, Tiffany C. Scharschmidt
{"title":"Commensal-myeloid crosstalk in neonatal skin regulates interleukin-1 signaling and cutaneous type 17 inflammation","authors":"Miqdad O. Dhariwala, Ricardo O. Carale, Andrea M. DeRogatis, Henry Rodriguez-Valbuena, Joy N. Okoro, Christina A. Ekstrand, Antonin Weckel, Victoria M. Tran, Irek Habrylo, Rio Barrere-Cain, Oluwasunmisola T. Ojewumi, Allison E. Tammen, Jessica Tsui, Saba Shaikh, Shivaram Yellamilli, Ahmed K. Aladhami, Robin Schwartz, John M. Leech, Geil R. Merana, Kamir J. Hiam-Galvez, Matthias Mack, Joanna Halkias, James M. Gardner, Rachel L. Rutishauser, Gabriela K. Fragiadakis, Matthew H. Spitzer, Alexis J. Combes, Tiffany C. Scharschmidt","doi":"10.1016/j.immuni.2026.01.005","DOIUrl":"https://doi.org/10.1016/j.immuni.2026.01.005","url":null,"abstract":"","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"44 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146072083","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}
Pub Date : 2026-01-28DOI: 10.1016/j.immuni.2025.12.010
Gillian Dunphy, Irene Adán-Barrientos, Irene Fernández-Delgado, Carolina Villarroya-Beltri, Ignacio Heras-Murillo, Elena Moya-Ruiz, Miguel Sánchez-Álvarez, Aitor Jarit-Cabanillas, Miguel A. del Pozo, Susana Guerra, Francisco Sánchez-Madrid, David Sancho
{"title":"A type I interferon-mitochondrial axis regulates efferocytosis and interferon-stimulated gene induction in macrophages","authors":"Gillian Dunphy, Irene Adán-Barrientos, Irene Fernández-Delgado, Carolina Villarroya-Beltri, Ignacio Heras-Murillo, Elena Moya-Ruiz, Miguel Sánchez-Álvarez, Aitor Jarit-Cabanillas, Miguel A. del Pozo, Susana Guerra, Francisco Sánchez-Madrid, David Sancho","doi":"10.1016/j.immuni.2025.12.010","DOIUrl":"https://doi.org/10.1016/j.immuni.2025.12.010","url":null,"abstract":"","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"279 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146071529","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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