Immunity

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.

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

Review @cp-immunity.bsky.social
A host-centric view of the microbiota metabolome
www.cell.com/immunity/ful...

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.

Online now: A host-centric view of the microbiota metabolome

Clonal persistence dominates homeostatic intestinal IgA responses @cp-immunity.bsky.social
www.cell.com/immunity/ful...

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.

Online now: Clonal persistence dominates homeostatic intestinal IgA responses

Notch3 destabilizes regulatory T cells to drive autoimmune neuroinflammation in multiple sclerosis Benamar et al. demonstrate that Notch3+ Treg cells are increased in multiple sclerosis and in EAE. They are induced in the gut by microbiota and translocate to the CNS to degenerate into pathogenic Th...

#WeekendRead! #FroendsOrFoes?! Benamar, Chatila &co identify @cp-immunity.bsky.social a #GutBrain axis leading to microbiota- & TLR-dependent induction of Notch3+ Tregs in the gut that in multiple sclerosis migrate to the CNS & interacting with microglia become pathogenic Th17 cells!

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.

Online now: Quantifying the waning of humoral immunity

Virus-specific CD8+ tissue-resident memory T cells trigger epithelial antiviral defenses via IFNγ @cp-immunity.bsky.social @emoryuniversity.bsky.social
www.cell.com/immunity/ful...

Deep profiling of human T cells defines compartmentalized clones and phenotypic trajectories across blood and tonsils @cp-immunity.bsky.social @ucirvine.bsky.social @tcellwhisperer.bsky.social
www.cell.com/immunity/ful...

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.

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

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, Sureshcha...

We are #absolutely #thrilled to #present @cp-immunity.bsky.social - Deep profiling of human T cells defines compartmentalized clones and phenotypic trajectories across blood and tonsils: Immunity www.cell.com/immunity/ful...

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.

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

Aging and immunity Time marches endlessly on … but what does that mean for the immune system? Here, investigators discuss how aging impacts the immune response and how i…

Our good friend @christophthaiss.bsky.social from @arcinstitute.org argues in the current @cp-immunity.bsky.social Voices that cytokine sensing by the brain may be key to decoding age-related decline, borrowing the concept of interoception from Erwin Schrödinger:
www.sciencedirect.co... 🧪

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.

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

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.

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

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.

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

Immunity by Cell Press | LinkedIn Immunity by Cell Press | 45 followers on LinkedIn. Cutting-edge research in immunology from around the world, and commentaries by thought leaders. | Immunity publishes the most important advances in i...

Immunity is now on LinkedIn! Follow us if you love #immunology! And if you don't already love immunology, maybe we'll change your mind 😀https://www.linkedin.com/company/immunity-cellpress

IL-9 enhancement of engineered CAR-T therapies
@cp-immunity.bsky.social @pennpress.bsky.social @xrtcell.bsky.social @stanforduniversity.bsky.social
www.cell.com/immunity/ful...
www.cell.com/immunity/ful...

Membrane integrity changes upon viral infection activate sphingomyelinase SMPDL3B to restrict cGAS-STING signaling via cGAMP degradation (Immunity 58, 2670–2684.e1–e10; November 11, 2025)

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

IgA generation from IgG1 precursors through sequential class switching @cp-immunity.bsky.social @yalepress.bsky.social @nupress.bsky.social
www.cell.com/immunity/ful... @stephanieeisen.bsky.social

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.

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

FOXP3 expression depends on cell-type-specific cis-regulatory elements and transcription factor circuitry FOXP3 is a transcription factor critical for immune homeostasis. Using a broad CRISPR toolkit, Umhoefer et al. elucidate the cis- and trans-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.

Online now: FOXP3 expression depends on cell-type-specific cis-regulatory elements and transcription factor circuitry

Glymphatics and meningeal lymphatics unlock the brain-immune code (Immunity 58, 1040–1051; May 13, 2025)

Online now: Glymphatics and meningeal lymphatics unlock the brain-immune code

Membrane integrity changes upon viral infection activate sphingomyelinase SMPDL3B to restrict cGAS-STING signaling via cGAMP degradation Wang et al. find that cell membrane stress upon viral infection induces expression and stabilization of host sphingomyelin phosphodiesterase acid-like 3B (SMPDL3B), which, in turn, degrades cGAMP to s...

#WeekendRead! #FriendOrFoes?! Zhang &co show @cp-immunity.bsky.social that herpes simplex virus #HSV1 exploits changes in membrane integrity to activate a GPI-anchored hydrolase which degrades cGAMP preventing #cGAS/#STING activation & favoring virus infection

www.cell.com/immunity/ful...