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People & Ideas

Yukiko Gotoh is a professor in the Department of Pharmaceutical Sciences at the University of Tokyo. Her lab studies the mechanisms that underlie the regulation of neural stem/progenitor cell fate during brain development and homeostasis.

Insights

In this issue of JEM, Allyn et al. provide mechanistic insights into the nuclear organization of the Tcrb locus that permits long-range genomic rearrangements.

The cytokine IL-23 plays important roles in intestinal barrier protection and integrity, but is also linked to chronic inflammation. In this issue of JEM, Ohara et al. provide clarity on the much-debated question of which cells produce IL-23.

Mural cells directly contact macrophages in the dural layer of the meninges to suppress pro-inflammatory phenotypes, including antigen presentation and lymphocyte differentiation. These mechanisms represent new targets for modulating CNS immune surveillance and pathological inflammation.

Reviews

Cancer Focus
In Special Collection: Cancer Immunotherapy Update 2024

The success of CAR-T cell therapies is dependent on effective cell manufacturing that impacts product safety, efficacy, and patient accessibility. Here, we discuss major process parameters of autologous CAR-T cell manufacturing, regulatory considerations, and emerging technologies in therapeutic cell manufacturing.

Technical Advances and Resources

In Special Collection: Immunology Update Winter 2024

Toll-like receptors 7 (TLR7) and 8 (TLR8) both recognize single-stranded RNA degradation products but give rise to different immune activation profiles. Here, Tong et al. develop TLR7-selective ligands by engineering 2′ sugar-modified bases into oligoribonucleotides to block RNase cleavage at specific phosphodiester bonds.

Articles

In Special Collection: Immunology Update Winter 2024

This study demonstrates that the precise mechanisms used to fold antigen receptor loci to position their V and (D)J gene segments in close spatial proximity determine how RAG-mediated synapsis and recombination of these segments occur across vast linear genomic distances.

An Il23aVenus strain reveals the EpCAM+ DCIR2+ cDC2s as a key cellular source of IL-23 at steady state and during infection with Citrobacter rodentium. Combined Notch2 and retinoic acid signals control the development of IL-23–producing cDC2s within gut-associated lymphoid tissues.

Min et al. show mural cells physically contact macrophages in the dura to regulate trafficking of CNS antigen-specific T cells. Mural cells are altered in presymptomatic EAE, and partially depleting mural cells activates dural macrophages and increases susceptibility to EAE.

In Special Collection: Barrier Immunity

Joulia et al. reveal a new mechanism whereby the transcription factor Eomes promotes CD4+ T cell accumulation in inflamed tissue through increased mitochondrial functions and resistance to cell death, therefore promoting the severity and chronicity of inflammation.

Acute aducanumab treatment triggers a concerted microglial response to amyloid, including increased peri-plaque recruitment and upregulation of activation, phagocytic, and immune-associated genes. However, discontinuation blunts microglial response up to 7 mo after the final treatment, even with the return of amyloid load.

The blood–DRG barrier is composed of endothelial cells with high permeability and is monitored by a subset of CD163+ perivascular macrophages, a process that is arteriovenously zonated. Vascular monitoring is abrogated by interfering with caveolar transcytosis in endothelial cells or by depleting CD163+ macrophages.

Bugaut et al. report a comparative study of MAIT cells in six species spanning 110 million years of evolution. They identify a deeply conserved transcriptional program characterized by coexpression of type-1 and type-17 effector genes. These ancestral features are further conserved in human iNKT cells.

This work reveals that human effector CD8 T cells not only mediate cytotoxicity but also promote tissue remodeling. The remodeling potential was demonstrated in different systems, including a primary organoid model and antigen-specific assays.

Paul Bastard,Adrian Gervais,Maki Taniguchi,Liisa Saare,Karita Särekannu,Tom Le Voyer,Quentin Philippot,Jérémie Rosain,Lucy Bizien,Takaki Asano,Marina Garcia-Prat,Alba Parra-Martínez,Mélanie Migaud,Miyuki Tsumura,Francesca Conti,Alexandre Belot,Jacques G. Rivière,Tomohiro Morio,Junko Tanaka,Etienne Javouhey,Filomeen Haerynck,Sotirija Duvlis,Tayfun Ozcelik,Sevgi Keles,Yacine Tandjaoui-Lambiotte,Simon Escoda,Maya Husain,Qiang Pan-Hammarström,Lennart Hammarström,Gloria Ahlijah,Anthony Abi Haidar,Camille Soudee,Vincent Arseguel,Hassan Abolhassani,Sabina Sahanic,Ivan Tancevski,Yoko Nukui,Seiichi Hayakawa,George P. Chrousos,Athanasios Michos,Elizabeth-Barbara Tatsi,Filippos Filippatos,Agusti Rodriguez-Palmero,Jesus Troya,Imran Tipu,Isabelle Meyts,Lucie Roussel,Sisse Rye Ostrowski,Laire Schidlowski,Carolina Prando,Antonio Condino-Neto,Nathalie Cheikh,Ahmed A. Bousfiha,Jalila El Bakkouri,COVID Clinicians,GEN-COVID Study Group,COVID Human Genetic Effort,Pärt Peterson,Aurora Pujol,Romain Lévy,Pierre Quartier,Donald C. Vinh,Bertrand Boisson,Vivien Béziat,Shen-Ying Zhang,Alessandro Borghesi,Andrea Pession,Evangelos Andreakos,Nico Marr,Alexios-Fotios A. Mentis,Trine H. Mogensen,Carlos Rodríguez-Gallego,Pere Soler-Palacin,Roger Colobran,Vallo Tillmann,Bénédicte Neven,Sophie Trouillet-Assant,Petter Brodin,Laurent Abel,Emmanuelle Jouanguy,Qian Zhang,Federico Martinón-Torres,Antonio Salas,Alberto Gómez-Carballa,Luis I. Gonzalez-Granado,Kai Kisand,Satoshi Okada,Anne Puel,Aurélie Cobat,Jean-Laurent Casanova

Auto-Abs neutralizing IFN-α and/or IFN-ω are found in about 10% of children with COVID-19 pneumonia. In uninfected children, auto-Abs neutralizing IFN-α2 are rarer (0.2%) than those neutralizing IFN-ω (2%). Auto-Abs against IFN-α thus confer a greater risk of COVID-19 pneumonia.

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