Articles

Lo and colleagues report that double-positive thymocytes from neonates express less Zap70 and show reduced Ca^2⁺/NFAT signaling compared to double-positive thymocytes from older thymi. This diminished Ca^2⁺ signaling alters negative selection for self-reactive TCRs, resulting in a cell-intrinsic temporal window for regulatory T versus conventional T cell development in the thymus.

Klein and colleagues characterize 04_A06, a new V_H1-2-encoded broadly neutralizing antibody that has marked breadth and potency against extended multiclade HIV-1 pseudovirus panels and can maintain full viral suppression in HIV-1-infected humanized mice.

Here the authors provide a deep tissue analysis of patients with autoimmune kidney diseases, identifying a conserved spatiotemporal immune program for the development of glomerular crescents and sclerosis.

DNA damage from chemotherapy can activate cGAS–STING and interferon pathways. Here, the authors show that cGAS–STING signaling is specific to DNA rich in CA repeats, whereas DNA not rich in CA repeats is detected by AIM2, resulting in opposing tumor immune responses.

Previous research has suggested that pDCs are required for an effective antiviral immune response, but direct experimental evidence to support this is lacking. Here Ngo et al. develop a pDC knockin mouse model and find that pDCs are dispensable for an antiviral immune response to mouse cytomegalovirus and may be detrimental during influenza or SARS-CoV-2 infection.

The authors spatially and functionally map innate lymphoid cells in the human female genital tract at homeostasis, uncovering tissue-specific and subset-specific distribution and functions, and rapid antiviral responses following HIV exposure.

Here the authors show how the DNA-sensing cGAS–STING pathway activates NF-κB and inflammatory gene expression with delayed kinetics via post-Golgi endolysosomal signaling.

Wang and colleagues show that specific DNA methylation profiles mark the ILC progenitors (ILCP) that would differentiate into ILC1, ILC2 or ILC3 subsets.

Wang and colleagues show that an AI-assisted designed peptide obstructs GSDMD pores and inhibits IL-1β and IL-18 release and pyroptosis.

Here the authors show a function for lymph nodes in the maintenance of effector T cell differentiation and function during chronic infection and checkpoint blockade, identifying a spatial component in the regulation of exhausted T cell fitness.

The thymus is sensitive to acute insults including infection, as well as to injury from chemotherapy and myeloablative conditioning before hematopoietic cell transplantation. Here, Granadier et al. describe a role for IL-18 in limiting thymic regeneration by stimulating NK cells, which then target thymic epithelial cells.

Erlich et al. show that soluble LTα and membrane-bound LTα1β2 lymphotoxins expressed by B cells play distinct roles to attenuate the pathology observed in ileitis.

Chen and colleagues show that type A cholesterol-dependent cytolysins, a group of bacteria pore-forming toxins, translocate to the trans-Golgi network to remodel it into a platform for NLRP3 activation.

Sawada et al. show simultaneous activation of the STING and lymphotoxin beta receptor signaling induces B cell-activating germinal center responses within tumor environment and enhances antitumor responses.

The authors identify pre-TCR as a key biomarker and therapeutic target in T-ALL. Targeting it with an anti-pTα antibody–drug conjugate inhibits leukemia-initiating cells and tumor growth in mice, offering promise for relapsed/refractory T-ALL treatment.

IRF3 initiates type I IFN transcription, and this is required for host defense. Here, Chen and colleagues show that RAD18 terminates the transcriptional activity of IRF3 and subsequently promotes the autophagic degradation of IRF3.

TCR-T cells are T cells engineered to express a specific T cell receptor. Here the authors present a TCR-T cell that targets CTNNB1-S37F, corresponding to a shared cancer driver mutation. This immunotherapy killed solid tumors when applied to a patient-derived xenograft model in mice.

Cui and colleagues identify the chromatin organizer protein SATB1 as a critical regulator of quiescence in stem-like progenitor CD8⁺ T cells that arise during chronic viral infection and cancer.

The authors show that the m⁶A reader protein YTHDF2 negatively regulates Th9 cell differentiation and function. Ablation of YTHDF2 promotes antigen-specific Th9 cell and CAR-Th9 cell antitumor activity in solid tumors.

Artis and colleagues show that enteric neurons produce CGRP-related ADM2 to promote intestinal tissue-protective functions in ILC2s.