ImmunityPub Date : 2026-10-09DOI: 10.1016/j.immuni.2026.09.013
Tenny Mudianto, Gabrielle R Berman, Kimberly Zaldana, Marta Schips, Niklas Schwan, Luan Firmino-Cruz, Jana Bilanovic, Ochapa Ibrahim, Vanessa Cristaldi, William S Foster, Lina Fikri, Sabrina Solis, Han Chen, Dimitri Kakabadse-Schmidt, Michael Cammer, Ramin Sedaghat Herati, Sergei B Koralov, Andrew David Miller, Michael Meyer-Hermann, Carla R Nowosad, Amanda W Lund
{"title":"Lymphatic constraint of germinal centers optimizes protective antibody responses.","authors":"Tenny Mudianto, Gabrielle R Berman, Kimberly Zaldana, Marta Schips, Niklas Schwan, Luan Firmino-Cruz, Jana Bilanovic, Ochapa Ibrahim, Vanessa Cristaldi, William S Foster, Lina Fikri, Sabrina Solis, Han Chen, Dimitri Kakabadse-Schmidt, Michael Cammer, Ramin Sedaghat Herati, Sergei B Koralov, Andrew David Miller, Michael Meyer-Hermann, Carla R Nowosad, Amanda W Lund","doi":"10.1016/j.immuni.2026.09.013","DOIUrl":"10.1016/j.immuni.2026.09.013","url":null,"abstract":"<p><p>Immunization strategies are central to pathogen control, where efficacy relies on antigen distribution and inflammatory context. Lymphatic vessels are necessary conduits for antigen transport that actively remodel in peripheral tissues and draining lymph nodes (LNs) in response to their inflammatory context. In this study, we found that inhibiting viral-induced lymphatic remodeling in skin and LNs prompted germinal center (GC) expansion but, paradoxically, decreased the protective antibody response. While GCs scaled proportionately, larger GCs failed to support proliferative bursts consistent with clonal selection due to impaired T-B cell interactions. Accordingly, follicle and GC size are evolutionarily conserved across diverse mammals despite increased LN size. Lymphatic vessels controlled GC size through two coordinated processes: lymphatic remodeling in infected skin limited viral transport to the LN, while the resulting permissive environment in the LN supported perifollicular lymphangiogenesis that constrained GC expansion.</p>","PeriodicalId":13269,"journal":{"name":"Immunity","volume":" ","pages":""},"PeriodicalIF":30.6,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13660447/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149148687","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}
ImmunityPub Date : 2026-10-08DOI: 10.1016/j.immuni.2026.09.011
Evi Paouri,Sarah Stanko,Nadia Gasmi,Gabriele Glusauskas,Valery Mao,Andrew Kwak,Stephanie Hsu,Sahar Sarmadi,Emily Huang,Aniruddha Das,Courtney Hershberger,Quinn Watercutter,Megan R. McMullen,Christopher Birck,Hope Burton,Hale Tobin,Anxhela Gjojdeshi,Julia Dziabis,Richa M. Hanamsagar,Daniel M. Rotroff,Richard A. Prayson,Staci D. Bilbo,Saba Valadkhan,Hod Dana,Laura E. Nagy,Dimitrios Davalos
{"title":"Microglia-mediated extracellular matrix disruption drives neuronal dysfunction, motor impairments, and sedation following alcohol abuse","authors":"Evi Paouri,Sarah Stanko,Nadia Gasmi,Gabriele Glusauskas,Valery Mao,Andrew Kwak,Stephanie Hsu,Sahar Sarmadi,Emily Huang,Aniruddha Das,Courtney Hershberger,Quinn Watercutter,Megan R. McMullen,Christopher Birck,Hope Burton,Hale Tobin,Anxhela Gjojdeshi,Julia Dziabis,Richa M. Hanamsagar,Daniel M. Rotroff,Richard A. Prayson,Staci D. Bilbo,Saba Valadkhan,Hod Dana,Laura E. Nagy,Dimitrios Davalos","doi":"10.1016/j.immuni.2026.09.011","DOIUrl":"https://doi.org/10.1016/j.immuni.2026.09.011","url":null,"abstract":"Alcohol abuse is the primary risk factor for alcohol use disorder (AUD), a leading cause of preventable morbidity and mortality worldwide. While direct effects of alcohol on neuronal function are well established, the role of microglia in acute and chronic neurological dysfunction in AUD remains underappreciated. Using mouse models of binge and high-intensity alcohol exposure and longitudinal in vivo imaging, we found that microglia exhibited acute and progressive morphological responses that preceded but paralleled ethanol-induced sedation. Ethanol also induced microglia-dependent extracellular matrix (ECM) disruption, synapse elimination, and reduced neuronal activity and density. Genetic deletion of microglial Myd88 protected against ethanol-induced microglial reactivity, neuronal damage and dysfunction, intoxication, and motor impairments by preventing ECM disruption. Frontal cortex ECM was similarly disrupted in human brain tissue from individuals with AUD. These findings identify microglia as cellular drivers of brain dysfunction following alcohol abuse and MyD88 as a critical therapeutic target for AUD.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"10 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149124072","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}
ImmunityPub Date : 2026-10-01DOI: 10.1016/j.immuni.2026.09.007
Marius Messemaker,Bjørn P.Y. Kwee,Živa Moravec,Sam de Paauw,Jos Urbanus,Daniel Álvarez-Salmoral,Jeroen Geerligs,Ren Xie,Rhianne Voogd,Ben Morris,Aurélie Guislain,Yaël Winkler,Connor A. Richterich,Maike Mussmann,Marijn Bakker,Maxime Steinmetz,Matyas Iras,Eric Marcus,Jonas Teuwen,Anastassis Perrakis,Roderick L. Beijersbergen,Wouter Scheper,Ton N. Schumacher
{"title":"Functional evaluation of TCR-pMHC pairs at scale allows in silico TCR reactivity prediction","authors":"Marius Messemaker,Bjørn P.Y. Kwee,Živa Moravec,Sam de Paauw,Jos Urbanus,Daniel Álvarez-Salmoral,Jeroen Geerligs,Ren Xie,Rhianne Voogd,Ben Morris,Aurélie Guislain,Yaël Winkler,Connor A. Richterich,Maike Mussmann,Marijn Bakker,Maxime Steinmetz,Matyas Iras,Eric Marcus,Jonas Teuwen,Anastassis Perrakis,Roderick L. Beijersbergen,Wouter Scheper,Ton N. Schumacher","doi":"10.1016/j.immuni.2026.09.007","DOIUrl":"https://doi.org/10.1016/j.immuni.2026.09.007","url":null,"abstract":"","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"2 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149090244","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}
ImmunityPub Date : 2026-10-01DOI: 10.1016/j.immuni.2026.09.009
Lutz Menzel,Hengbo Zhou,James W. Baish,Meghan J. O’Melia,Laurel B. Darragh,Derek N. Effiom,Emma Specht,Juliane Czapla,Pin-ji Lei,Johanna J. Rajotte,Lingshan Liu,Mohammad R. Nikmaneshi,Mohammad S. Razavi,Matthew G. Vander Heiden,Jessalyn M. Ubellacker,Lance L. Munn,Sana D. Karam,Genevieve M. Boland,Sonia Cohen,Timothy P. Padera
{"title":"Distant lymph nodes compensate for resected tumor-draining lymph nodes during cancer immunotherapy","authors":"Lutz Menzel,Hengbo Zhou,James W. Baish,Meghan J. O’Melia,Laurel B. Darragh,Derek N. Effiom,Emma Specht,Juliane Czapla,Pin-ji Lei,Johanna J. Rajotte,Lingshan Liu,Mohammad R. Nikmaneshi,Mohammad S. Razavi,Matthew G. Vander Heiden,Jessalyn M. Ubellacker,Lance L. Munn,Sana D. Karam,Genevieve M. Boland,Sonia Cohen,Timothy P. Padera","doi":"10.1016/j.immuni.2026.09.009","DOIUrl":"https://doi.org/10.1016/j.immuni.2026.09.009","url":null,"abstract":"","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"24 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149090241","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}
ImmunityPub Date : 2026-09-30DOI: 10.1016/j.immuni.2026.09.003
Amina Sayed, Tomoyoshi Yamano, Madlen Steinert, Elisabetta Petrozziello, Iliana Siamishi, Christine Federle, Rahvira Kalaycii, Sebastian Schulz, Katharina Pracht, Linus Rinke, Van Duc Dang, Florentina Porsch, Jasmin Huber, Seren Baygün, David Machač, Simon Schäfer, Dominik Filipp, Anne Krug, Hans-Martin Jäck, Christoph J. Binder, Andreas Weinhäusel, Marc Schmidt-Supprian, Simon Fillatreau, Tobias Straub, Thomas H. Winkler, Wolfgang Schuh, Ludger Klein
{"title":"Aire is a cell-intrinsic regulator of natural IgM-secreting cells","authors":"Amina Sayed, Tomoyoshi Yamano, Madlen Steinert, Elisabetta Petrozziello, Iliana Siamishi, Christine Federle, Rahvira Kalaycii, Sebastian Schulz, Katharina Pracht, Linus Rinke, Van Duc Dang, Florentina Porsch, Jasmin Huber, Seren Baygün, David Machač, Simon Schäfer, Dominik Filipp, Anne Krug, Hans-Martin Jäck, Christoph J. Binder, Andreas Weinhäusel, Marc Schmidt-Supprian, Simon Fillatreau, Tobias Straub, Thomas H. Winkler, Wolfgang Schuh, Ludger Klein","doi":"10.1016/j.immuni.2026.09.003","DOIUrl":"https://doi.org/10.1016/j.immuni.2026.09.003","url":null,"abstract":"The autoimmune regulator (Aire) promotes T cell tolerance through promiscuous gene expression in medullary thymic epithelial cells, but growing evidence points to additional roles beyond thymic tolerance. We show that antibody-secreting cells (ASCs) in the spleen and bone marrow expressed Aire, with highest expression in immunoglobulin M (IgM)<ce:sup loc=\"post\">+</ce:sup> cells. These Aire<ce:sup loc=\"post\">+</ce:sup>IgM<ce:sup loc=\"post\">+</ce:sup> cells displayed hallmarks of natural IgM-secreting cells: they were T cell independent, exhibited distinct repertoire features, and arose primarily from B-1a and marginal zone B cells. While innate signals were sufficient <ce:italic>in vitro</ce:italic> to promote plasmablast differentiation, synergistic B cell survival and growth factor signaling through B cell-activating factor (BAFF) or APRIL was required to robustly induce Aire, revealing a previously unrecognized tumor necrosis factor (TNF) superfamily pathway controlling Aire induction. Aire did not promote promiscuous gene expression in these cells, but intrinsically limited their numbers, identifying a role in homeostatic regulation of natural polyreactive IgM in steady state rather than self-tolerance.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"2 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149085152","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}
ImmunityPub Date : 2026-09-30DOI: 10.1016/j.immuni.2026.09.023
Jenna M. Kastenschmidt, Suhas Sureshchandra, Aarti Jain, Jenny E. Hernandez-Davies, Rafael de Assis, Zachary W. Wagoner, Andrew M. Sorn, Mahina Tabassum Mitul, Aviv I. Benchorin, Elizabeth Levendosky, Gurpreet Ahuja, Qiu Zhong, Douglas Trask, Jacob Boeckmann, Rie Nakajima, Algimantas Jasinskas, Naresha Saligrama, D. Huw Davies, Lisa E. Wagar
{"title":"Influenza vaccine format mediates distinct cellular and antibody responses in human immune organoids","authors":"Jenna M. Kastenschmidt, Suhas Sureshchandra, Aarti Jain, Jenny E. Hernandez-Davies, Rafael de Assis, Zachary W. Wagoner, Andrew M. Sorn, Mahina Tabassum Mitul, Aviv I. Benchorin, Elizabeth Levendosky, Gurpreet Ahuja, Qiu Zhong, Douglas Trask, Jacob Boeckmann, Rie Nakajima, Algimantas Jasinskas, Naresha Saligrama, D. Huw Davies, Lisa E. Wagar","doi":"10.1016/j.immuni.2026.09.023","DOIUrl":"https://doi.org/10.1016/j.immuni.2026.09.023","url":null,"abstract":"","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"84 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149085151","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}
ImmunityPub Date : 2026-09-29DOI: 10.1016/j.immuni.2026.09.002
Hannah Van Hove,Jonathan Bastos,Daliya Kancheva,Mónica Vara-Pérez,Marie-France Dorion,Frederike Westermann,Can Ulutekin,Hadis Shakeri,Leen Ali,Ayla Line Lievens,Maud Mayoux,Nele Sterczyk,Francesca Biscu,Laura Meysman,Isabelle Scheyltjens,Karen De Vlaminck,Ana Rita Pombo Antunes,Wiebke Mildenberger,Lukas Amann,Diego Gomez-Nicola,Ilse Smolders,Sonia Tugues,Florent Ginhoux,Marco Prinz,Charlotte L. Scott,Burkhard Becher,Jo A. Van Ginderachter,Melanie Greter,Kiavash Movahedi
{"title":"Microglia with distinct origins and non-canonical phenotypes coexist within the border-like niche of the brain’s circumventricular organs","authors":"Hannah Van Hove,Jonathan Bastos,Daliya Kancheva,Mónica Vara-Pérez,Marie-France Dorion,Frederike Westermann,Can Ulutekin,Hadis Shakeri,Leen Ali,Ayla Line Lievens,Maud Mayoux,Nele Sterczyk,Francesca Biscu,Laura Meysman,Isabelle Scheyltjens,Karen De Vlaminck,Ana Rita Pombo Antunes,Wiebke Mildenberger,Lukas Amann,Diego Gomez-Nicola,Ilse Smolders,Sonia Tugues,Florent Ginhoux,Marco Prinz,Charlotte L. Scott,Burkhard Becher,Jo A. Van Ginderachter,Melanie Greter,Kiavash Movahedi","doi":"10.1016/j.immuni.2026.09.002","DOIUrl":"https://doi.org/10.1016/j.immuni.2026.09.002","url":null,"abstract":"Circumventricular organs (CVOs) are small brain regions lacking a blood-brain barrier, giving neurons direct access to blood-borne signals, yet how these microenvironments shape the origin and phenotype of local macrophages remains unclear. Using multi-omics, we characterized the immune landscape of two CVOs, the area postrema (AP) and median eminence (ME), revealing brain-border-like environments with a unique macrophage compartment. CVO microglia showed a distinct, heterogeneous phenotype, including a CLEC7Ahigh myelin-associated subset in the ME, shaped by ageing and metabolism. CVO microglia were ontogenically diverse: fetal monocytes entered the CVOs perinatally and generated long-lived monocyte-derived microglia that fully adopted a yolk-sac-derived microglia identity. After depletion, CVO microglia were repopulated by local Sall1high cells but also by monocytes in the AP. Similarly, perivascular CVO border-associated macrophages displayed a distinct phenotype and origin. Our findings establish CVOs as specialized immune niches that shape local macrophages, reflecting the immune and metabolic demands of these environments.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"10 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149070983","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}
ImmunityPub Date : 2026-09-24DOI: 10.1016/j.immuni.2026.09.001
Ganesh R.R. Visweswaran,Pooya Mahdavi,Kamalakannan Vijayan,Francis B. Ntumngia,Bart L. Staker,Samantha J. Barnes,Pradeep A. Subramani,Andrew Raappana,Nicholas Dambrauskas,Elizabeth K.K. Glennon,Surendra K. Kolli,Madison M. Ogbondah,Alexander Watson,Nelly Camargo,Banumathi Sankaran,Pongsakorn Thawornpan,Rachaneeporn Jenwithisuk,Peter J. Myler,Stefan H.I. Kappe,Wanlapa Roobsoong,Patchanee Chootong,Jetsumon Sattabongkot,Alexis Kaushansky,Vladimir Vigdorovich,John H. Adams,D. Noah Sather
{"title":"Targeting a site of vulnerability on circumsporozoite protein inhibits Plasmodium vivax malaria infection","authors":"Ganesh R.R. Visweswaran,Pooya Mahdavi,Kamalakannan Vijayan,Francis B. Ntumngia,Bart L. Staker,Samantha J. Barnes,Pradeep A. Subramani,Andrew Raappana,Nicholas Dambrauskas,Elizabeth K.K. Glennon,Surendra K. Kolli,Madison M. Ogbondah,Alexander Watson,Nelly Camargo,Banumathi Sankaran,Pongsakorn Thawornpan,Rachaneeporn Jenwithisuk,Peter J. Myler,Stefan H.I. Kappe,Wanlapa Roobsoong,Patchanee Chootong,Jetsumon Sattabongkot,Alexis Kaushansky,Vladimir Vigdorovich,John H. Adams,D. Noah Sather","doi":"10.1016/j.immuni.2026.09.001","DOIUrl":"https://doi.org/10.1016/j.immuni.2026.09.001","url":null,"abstract":"Circumsporozoite protein (CSP) is the most abundant Plasmodium sporozoite surface antigen. It is the major component of licensed Plasmodium falciparum vaccines and, hence, is the logical lead candidate for Plasmodium vivax (P. vivax) vaccines. However, our limited knowledge of protective B cell epitopes on P. vivax CSP remains a major roadblock. Here we identified two Plasmodium vivax CSP (PvCSP) B cell epitopes, PvCSP-A and PvCSP-B/NAGG, by screening inhibitory plasma from P. vivax-infected individuals. The epitopes were located in the N- and C-terminal regions of PvCSP, respectively, and were distinct from the canonical central repeat region epitope. We isolated a monoclonal antibody, GRAM-4, that recognized the PvCSP-B/NAGG epitope and mediated potent inhibition of traversal, hepatocyte invasion, and liver-stage development in vitro, confirming PvCSP-B/NAGG as a genuine neutralization target. Structural resolution of the GRAM-4:PvCSP-B/NAGG interaction at 2.65 Å revealed the molecular basis of epitope recognition, providing a blueprint for PvCSP vaccine development.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"11 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149027571","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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