Issues

PGD₂ released after NAIP-NLRC4 inflammasome activation in tuft cells signals onto ILC3s and mediates host defense mechanisms against Salmonella Typhimurium within the small intestine. Tuft cells therefore not only promote immune reactions against parasites, but also bacteria.

Madsen et al. identify a neuraminidase-targeting human monoclonal antibody (mAb-297) induced by seasonal influenza vaccination that broadly protects against multiple influenza A and B strains, including avian H5N1. This study highlights the potential of developing more broadly protective influenza vaccines through targeting neuraminidase.

BRCA1 is upregulated in the kidney after chronic kidney disease. BRCA1 exon 11 deletion from proximal tubular epithelial cells (PTECs) protects mice from kidney fibrosis. BRCA1 downregulation by siRNA and shRNA decreases pro-fibrotic signaling in PTECs by decreasing G2/M cell cycle arrest and senescence.

Radiotherapy not only kills tumors but also shapes immunity. This study reveals that in radioresistant tumors, clinically relevant radiotherapy induces GM-CSF secretion, driving immunosuppressive monocyte-derived dendritic cells and regulatory T cells. Targeting monocyte differentiation and GM-CSF may enhance radiotherapy efficacy.

This study demonstrates that impaired T cell receptor–induced CARD11-dependent JNK signaling results in upregulation of GATA3 and NFAT2, two key proteins in the development of T_H2 cells, identifying a novel molecular mechanism by which dominant interfering CARD11 variants spur the development of atopic disease.

Jang et al. report that when the activating Kras mutation arises in hematopoietic stem cells, it causes the expansion and reprogramming of multipotent progenitors. These hypercompetitive progenitors lack self-renewal but rapidly spread the mutation throughout the blood system.

This work describes a previously uncharacterized external, experimentally accessible secondary lymphoid organ in the zebrafish located above the pectoral fin. The authors demonstrate how this organ can be used to image immune cell trafficking and interaction with surrounding tissues in and ex vivo.

This study identifies MYO1F as a pivotal regulator of the immunosuppressive capabilities and expansion of tumor-associated neutrophils during cancer progression. By elucidating a novel regulatory mechanism involving MYO1F, we offer valuable insights into potential indicators of ICB efficacy.

Autoantibodies neutralizing IFN-Is exacerbate severe viral diseases such as COVID-19. Here, the authors identify IFN-I regions commonly targeted by these autoantibodies, characterize the pathogenic mechanism of autoantibody action, and develop a proof-of-concept inhibitory decoy strategy to alleviate IFN-I autoantibody effects.

Using precise spatial tracking of tumor cell populations, this study demonstrates tumor cells shape their immune microenvironment on a highly localized spatial scale. CX3CL1-producing tumor cells attract suppressive macrophages to their vicinity, dampening T cell function and driving immunotherapy resistance.

This review discusses how aging and diet influence the metabolic reprogramming of the tumor–immune microenvironment, contributing to cancer progression and immune evasion. It highlights the impact on T-cell function and explores therapeutic strategies to restore antitumor immunity by targeting metabolic pathways.

Fungi pose a growing health threat, with rising antifungal resistance. Deciphering the genetic and molecular bases of human immunity to fungi in the non-iatrogenic settings, through the study of individuals and at-risk populations, helps define pathways tractable for precision therapy.

Maladaptive repair following kidney injury leads to the development of kidney disease. In this issue of JEM, Ajay et al. uncover the role of breast cancer susceptibility gene 1 (BRCA1) in cell cycle arrest, DNA damage, and cell senescence, preventing maladaptive repair.

Castranova et al. describe a new secondary lymphoid organ found in fish. Translucent and externally located adjacent to the pectoral fin, the axillary lymphoid organ (ALO) likely facilitates interactions between T, B, and macrophage cells, arguing it may function in adaptive immune cell communication and activation.

Laura Mackay is a professor and Immunology Theme Leader at the Doherty Institute at the University of Melbourne. Her lab investigates memory T cells, including their development, the role tissue-resident memory T cells play in cancer, autoimmune diseases, and barrier immunity, as well as ways in which these cells may be used therapeutically to treat various pathologies.