Issues

T cell exhaustion limits antiviral response. Targeting BCOR and ZC3H12A potently enhances the stemness and functionality of CD8 T cells in chronic viral infections, reversing T cell exhaustion and improving antiviral immunity.

A high-salt diet increases Bacteroides abundance and intestinal propionate, activating the HIF-1α–TGF-β1 axis and promoting glioma invasion. This study reveals new insights into how gut microbiota and their metabolites contribute to glioma development and progression.

Vaseghi-Shanjani et al. report the first human disease caused by a genetic alteration in ThPOK, establishing ThPOK as essential for human T cell development and the regulation of fibrosis. They link ThPOK dysfunction to immune dysregulation, T cell defects, and fibrosis.

Immunization generates concentration gradients of antigens and inflammation across interconnected chains of LNs. These gradients cause preferential programing of effector versus memory precursor T cells within individual LNs, together regulating the magnitude and heterogeneity of adaptive immunity.

The colonic mucus barrier and sentinel goblet cells protect the distal gut from microbial challenges. This study demonstrates that microbial colonization drives sequential development of both of these barrier mechanisms in the pre-weaning intestine, setting the stage for the increased microbial burden associated with weaning.

The manuscript reports on patient with a USP5 mutation that gives rise to insensitivity to pain. The patient’s pathology is phenocopied in a knock-in mouse model and appears to be due to a dominant-negative loss of function of deubiquitinase activity.

Using a multiomics approach, the authors identify immunopathological, microbial, and metabolomic signatures of inflammatory bowel disease in humans and mice with partial RAG deficiency and identify a curative role for bone marrow transplantation.

Zhang et al. demonstrate that the expression of a mutated CARMIL2 protein in CD28-deficient mice induces most of the developmental and functional consequences known to result from CD28 costimulation and in turn triggers potent tumor-specific T cell responses resistant to PD-1 and CTLA-4 blockade.

This work identifies RORγt-lineage APCs as mediators of oral tolerance. The authors spatiotemporally map these APCs and define the identity and lineage of RORγt extrathymic Aire-expressing cells and their role in dietary antigen-specific regulatory T cell induction.

Cardoso et al. show that DNGR-1–deficient pre-cDCs display cell-intrinsic alterations in their ability to colonize peripheral organs. Their findings highlight an unexpected role for innate immune receptors in regulating cDCpoiesis.

Our findings reveal a divergent transcriptomic and epigenetic landscape between conventional and inflationary memory responses in spleen and liver during latent infection, while these molecular programs converge early in salivary glands, highlighting how the dynamics of memory CD8⁺ T cell responses are distinct between tissues.

Sun et al. highlight eTACs as a key component in the group of RORγt⁺ antigen-presenting cells acting in the induction of RORγt⁺ pTregs specific to food antigens, while implicating DCs in the generation of RORγt⁻ pTregs.