Latest Articles

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Immunity · Dec 05, 2025

A chemical agonist and the Golgi-resident lipid PI4P activate STING by inducing transmembrane helix rearrangement

While the phospholipid PI4P is implicated in STING activation, its molecular mechanism has remained elusive. Han et al. reveal that PI4P cooperates with the transmembrane agonist GNE-6468 to activate the STING immune response, highlighting its therapeutic potential for immunotherapy.

biology

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Immunity · Dec 02, 2025

A host-centric view of the microbiota metabolome

Our current understanding of microbial-host communication is largely based on context-dependent examples and anecdotes. Yamada and Palm present a teleological framework that organizes microbial metabolites based on their impacts on the host. These fundamental principles of host-microbe interplay enhance our perspectives of how microbial metabolites influence host immunity and beyond.

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Immunity · Dec 01, 2025

Clonal persistence dominates homeostatic intestinal IgA responses

Gut plasma cells secrete IgA, which prevents infections, neutralizes toxins, and regulates the gut microbiota. Simons et al. demonstrate that stable IgA production results not from the persistence of individual plasma cells but rather a continuous dynamic renewal of the gut plasma cell population through diversification of large B cell clones.

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Immunity · Nov 28, 2025

Quantifying the waning of humoral immunity

Memory is a central feature of the adaptive immunity. Saha et al. quantitatively model humoral memory and find that the pattern of waning of antibodies is better described by a power-law model rather than models with exponential waning. Their findings suggest that protective antibody titers may be maintained for longer than previously estimated.

biology

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Immunity · Nov 26, 2025

Deep profiling of human T cells defines compartmentalized clones and phenotypic trajectories across blood and tonsils

Human T cell responses are often studied using blood, yet most T cells reside in tissues. By comparing T cell receptor repertoires from millions of T cells from autologous tonsils and blood, Sureshchandra et al. demonstrate limited clonal, phenotypic, and functional overlap between compartments, underscoring the importance of tissue context when extrapolating blood-based analyses to overall T cell repertoire.

biology

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Immunity · Nov 26, 2025

Human lung CD8+tissue-resident memory T cell-derived interferon-γ orchestrates subset-specific antiviral programming in airway epithelial cells

Mattingly et al. use human lung cells to show that virus-specific CD8+tissue-resident memory T cells trigger epithelial antiviral defenses via IFNγ. This early protective response varies by epithelial subset, restricts influenza infection, and highlights the importance of Trm-epithelial cell crosstalk in mediating respiratory virus control.

biology

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Immunity · Nov 24, 2025

Topography of the HLA-A protein enforces shared and convergent immunodominant B cell and antibody alloresponses in transplant recipients

Donor-specific antibodies against mismatched HLA proteins cause allograft failure, but the structural epitopes recognized by these antibodies are not well defined. Killian et al. identify immunodominant HLA-A∗01:01 epitopes that are localized specifically on the HLA crown and conserved across transplant recipients. These findings provide a framework for understanding the immunogenicity of non-self in organ transplant rejection.

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Immunity · Nov 21, 2025

Membrane integrity changes upon viral infection activate sphingomyelinase SMPDL3B to restrict cGAS-STING signaling via cGAMP degradation

(Immunity58, 2670–2684.e1–e10; November 11, 2025)

biology

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Immunity · Nov 21, 2025

IL-9 as a naturally orthogonal cytokine with optimal JAK/STAT signaling for engineered T cell therapy

Cytokines optimize and fine-tune effector T cell responses. Here, Jiang et al. utilize IL-9, with scarce receptor expression in normal tissues, to boost IL-9R engineered T cells for cancer therapy. IL-9 signaling initiates a unique STAT activation pattern, including STAT4, that modulates T cell states for effective anti-tumor responses.

biology

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Immunity · Nov 21, 2025

IL-9 signaling redirects CAR T cell fate toward CD8+memory and CD4+cycling states, enhancing antitumor efficacy

Castelli et al. show that incorporating interleukin-9 (IL-9) signaling reprograms chimeric antigen receptor (CAR) T cells to expand, persist, and resist dysfunction in solid tumors. This strategy improves antitumor activity at lower doses, suggesting a promising way to enhance the effectiveness of CAR T cell therapies against solid cancers.

biology

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Immunity · Nov 17, 2025

Sequential class switching generates antigen-specific gut IgA from IgG1 B cells

IgA antibodies protect mucosal surfaces from foreign antigens. Siniscalco et al. identify germinal center (GC)-independent and GC-derived pathways of gut IgA generation following immunization. Siniscalco et al. also identify IgA generation from IgG1 precursors through sequential class switching. These findings link systemic and mucosal antibodies for multi-pronged host protection.

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Immunity · Nov 13, 2025

Glymphatics and meningeal lymphatics unlock the brain-immune code

(Immunity58, 1040–1051; May 13, 2025)

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Immunity · Nov 13, 2025

FOXP3 expression depends on cell-type-specificcis-regulatory elements and transcription factor circuitry

FOXP3 is a transcription factor critical for immune homeostasis. Using a broad CRISPR toolkit, Umhoefer et al. elucidate thecis- andtrans-regulatory circuitry governing FOXP3 expression in human Treg and Tconv cells, including characterization of a repressive CRE that limits expression of FOXP3 in Tconv cells.

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Immunity · Nov 07, 2025

Highly functional and prolonged germinal center T follicular helper cell responses are associated with enhanced neutralizing antibody development

The dynamics of antigen-specific Tfh responses during extended germinal center reactions are not well characterized. Marina-Zárate et al. show that vaccine-specific Tfh cells in the lymph node undergo robust early expansion, sustained proliferative capacity, months-long persistence without exhaustion, and functional specialization into subsets associated with enhanced germinal center activity and humoral immunity.

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