Reviews & Analysis

Deletion of TFAM, the master regulator of mitochondrial transcription and translation, limits germinal center reactions. Notably, TFAM affects several processes beyond bioenergetics, such as migration, signaling, somatic hypermutation and redox balance.

New work from Udeochu, Amin, Huang, and colleagues provides mechanistic insights into how the tau protein engages the cGAS–STING pathway to elicit antiviral responses in Alzheimer’s disease. This signaling axis diminishes the MEF2C transcriptional network in neurons critical for maintaining cognitive function.

A blood single-cell atlas of human sepsis identifies subsets of immune-suppressive neutrophils in people at high risk.

Orthogonal engineering of adoptively transferred CD8⁺ T cells to co-express two cytokines — an IL-2Rβ/γ-biased IL-2 variant and the proinflammatory alarmin IL-33 — induces an exhaustion-resistant synthetic cell state with potent anti-tumor efficacy in the absence of host pre-conditioning.

APLAID is a very rare autoinflammatory disease thought to be caused by mutations in PLCG2. A mouse model of APLAID recapitulates clinical features of the disease, and identifies a crucial function for G-CSF that might be targeted therapeutically.

The immune system is not immune to sex differences. New research now uncovers the molecular mechanisms that underlie sex-based differences during antiviral immune responses.

Mononuclear phagocyte proliferation is thought to be limited to myeloid progenitor cells and mature macrophages. However, availability within an interstitial macrophage niche permits the proliferation of monocytes in the lung before macrophage differentiation.

Capturing cell organization in the tumor microenvironment using spatial proteomics can provide insight into the disease. A pair of studies applying this to advanced lung and brain tumors identifies organizational immune hallmarks that are associated with patient outcomes.

Antibody dynamics resulting from sequential immunization are complex, limiting the study of concepts such as ‘original antigenic sin’. Here, molecular fate-mapping defines an ‘addiction’ of boosted antibodies to primary clones, and OAS-like suppression of new clones, to a degree inversely related to boosting antigenic distance.

Taking advantage of intersectional genetics, Valente et al. report a novel strategy for tracking plasmacytoid dendritic cells (DCs) that enables their discrimination from conventional DCs and plasmacytoid DC–like cells, as well as transitional DCs.

The NLRP10 protein is found to form an inflammasome complex in response to mitochondrial damage. Loss of NLRP10 from colonic epithelia promotes inflammatory bowel disease in a mouse model, while a variant predisposing to atopic dermatitis also shows loss of function.

Several panels of naturally arising antibodies against specific chemokines are closely correlated with various favorable COVID-19 outcomes, raising an opportunity to target the chemokine system for long COVID treatment.

Dendritic-cell-biased thymic seeding progenitors provide stromal support for early T cell development through the expression of membrane-bound TNF.

A new study by Zhou et al. identifies a unique microglia state in Nasu-Hakola disease and new potential therapeutic targets.

A serendipitous behavioral observation in a mouse line led to the discovery that macrophages modulate acute pain. The macrophage-derived protein SNX25 sets the threshold for acute pain through tonic NGF signaling to cutaneous sensory neurons.

Research shows that Vδ1 and Vδ3 γδ T cells that express PD-1 and display potent cytotoxic functions are key immune responders in HLA-class-I-negative colon cancers subjected to immune checkpoint blockade therapy.

In addition to the acute phase of SARS-CoV-2 infection, a significant percentage of patients experience a prolonged illness with varying symptomatology. Longitudinal SARS-CoV-2 patient-centric immunologic, inflammatory and metabolic data collection has allowed the generation of a composite signature to predict recovery.

T_H17 cells combat infection but can also drive pathological inflammation. A T_H17 cell NLRP3–caspase-8–caspase-3–GSDME axis is now shown to release the alarmin IL-1α without triggering cell death.

Human resident memory T (T_RM) cells clonally segregate in distinct tissues, with gene expression signatures tailored to those sites. Hence, beyond a shared language of residency, T_RM cells may acquire local dialects to provide site-specific immunity.

A specialized subset of iNKT cells populates the skin in early life, where their supply of transferrin regulates iron metabolism to promote hair follicle development.