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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.


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.


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.


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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