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Fabian M.P. Kaiser, Sarah Gruenbacher, Maria Roa Oyaga, Enzo Nio, Markus Jaritz, Qiong Sun, Wietske van der Zwaag, Emanuel Kreidl, Lydia M. Zopf, Virgil A.S.H. Dalm, Johan Pel, Carolin Gaiser, Rick van der Vliet, Lucas Wahl, André Rietman, Louisa Hill, Ines Leca, Gertjan Driessen, Charlie Laffeber, Alice Brooks, Peter D. Katsikis, Joyce H.G. Lebbink, Kikuë Tachibana, Mirjam van der Burg, Chris I. De Zeeuw, Aleksandra Badura, Meinrad Busslinger
A mouse model carrying biallelic Pax5 mutations identified in a patient with hypogammaglobulinemia and autism spectrum disorder shows a B cell developmental arrest and autistic-like behavior caused by abnormal development of the cerebellum and loss of ventral midbrain GABAergic neurons.
Technical Advances and Resources
Sara A. Rubin, Chloé S. Baron, Cecilia Pessoa Rodrigues, Madeleine Duran, Alexandra F. Corbin, Song P. Yang, Cole Trapnell, Leonard I. Zon
Single-cell RNA sequencing of zebrafish hematopoiesis provides new insights into zebrafish B- and T-cell development and cellular diversity within the primary lymphoid organs (kidney marrow and thymus). This work advances the current understanding of zebrafish immunology and will facilitate future genetic and developmental studies.
Brief Definitive Report
Danielle Karo-Atar, Shaida Ouladan, Tanvi Javkar, Loick Joumier, Macy K. Matheson, Sydney Merritt, Susan Westfall, Annie Rochette, Maria E. Gentile, Ghislaine Fontes, Gregory J. Fonseca, Marc Parisien, Luda Diatchenko, Jakob von Moltke, Mohan Malleshaiah, Alex Gregorieff, Irah L. King
Karo-Atar et al. demonstrate direct regulation of the intestinal stem cell compartment by an enteric helminth, resulting in expansion of fetal-like stem cells and inhibition of secretory cells. They establish how a helminth parasite co-opts a tissue development program to counter type 2 immune-mediated expulsion.
Brief Definitive Report
Malika Hale, Jason Netland, Yu Chen, Christopher D. Thouvenel, Katherine Nabel Smith, Lucille M. Rich, Elizabeth R. Vanderwall, Marcos C. Miranda, Julie Eggenberger, Linhui Hao, Michael J. Watson, Charles C. Mundorff, Lauren B. Rodda, Neil P. King, Miklos Guttman, Michael Gale, Jr, Jonathan Abraham, Jason S. Debley, Marion Pepper, David J. Rawlings
Using monoclonal antibodies built from SARS-CoV-2–specific memory B cells, Hale et al. demonstrate that IgM antibodies outperform IgG in neutralization assays against mutated variants. The authors suggest that IgM antibodies may be useful therapeutically, and that IgM memory B cells may be underappreciated protectors against rapidly evolving pathogens.
Technical Advances and Resources
Michael Beckstette, Chia-Wen Lu, Susanne Herppich, Elia C. Diem, Anna Ntalli, Aaron Ochel, Friederike Kruse, Beate Pietzsch, Katrin Neumann, Jochen Huehn, Stefan Floess, Matthias Lochner
In this study, the authors perform a genome-wide methylation analysis to define epigenetic signatures for murine ILCs and to assess similarities and differences to CD4+ T cells. Models of IL-33–mediated inflammatory challenge reveal tissue-specific epigenetic changes within ILC2 signature regions.
Article
Yu Rebecca Miao, Kaushik Thakkar, Can Cenik, Dadi Jiang, Kazue Mizuno, Chenjun Jia, Caiyun Grace Li, Hongjuan Zhao, Anh Diep, Yu Xu, Xin Eric Zhang, Teddy Tat Chi Yang, Michaela Liedtke, Parveen Abidi, Wing-sze Leung, Albert C. Koong, Amato J. Giaccia
Miao et al. demonstrate the dichotomous activities of APRIL and BAFF in MM and DLBCL, which can be safely targeted by an engineered decoy receptor designed to trap both ligands with ultra-high binding affinity.
Article
Shen-zhao Lu, Yue Wu, Yong-shun Guo, Pei-zhou Liang, Shu Yin, Yan-qing Yin, Xiu-li Zhang, Yan-Fang Liu, Hong-yan Wang, Yi-chuan Xiao, Xin-miao Liang, Jia-wei Zhou
Astrocyte activation is associated with inflammatory demyelination in multiple sclerosis. Lu et al. show the key role for DRD2/PTS/PKCδ axis in the modulation of astrocyte activation. Its therapeutic inhibition may provide a potent lever to alleviate autoimmune diseases.

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Issue Cover
Current Issue
Volume 219,
Issue 8,
1 August 2022
Reviews & Opinions
Insights
Sandro Da Mesquita
In this issue, Jacob et al. employ imaging techniques to provide a more comprehensive chart of the meningeal lymphatic vasculature and draw a parallel for lymphatic drainage of cerebrospinal fluid in mice and humans.
Perspective
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Microglia, the tissue macrophages of the central nervous system, use phagocytosis of loosely organized amyloid beta (Aβ) to construct dense-core plaques, one of the defining histopathological features of Alzheimer’s disease. The biology of this process parallels macrophage construction of granulomas in tuberculosis and other settings.
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Gut dysbiosis has long been associated with the development of Crohn's disease and other gastrointestinal disorders. Otake-Kasamoto et al. report that dysbiotic microbiota–derived bioactive lipids, lysophosphatidylserines, can promote pathological Th1 cell responses through inducing metabolic reprogramming and epigenetic changes.

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