Reviews & Analysis

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.

Many immune cell subsets move in an amoeboid fashion and do not require strong adhesive interactions with their surrounding when moving through interstitial tissue spaces. In stark contrast, we show that mast cells critically depend on integrin-mediated adhesion and interactions with the extracellular matrix to enable slow migration and site-specific positioning in tissues.

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.

The US National Institute of Allergy and Infectious Diseases hosted a two-day virtual workshop on skin microbial communities and their interactions with the host immune system in health and disease. The aim of the workshop was to evaluate the current state of knowledge in the field and identify gaps, challenges, and future directions.

Regulatory T (T_reg) cells respond to interferon-γ (IFNγ) during viral infection and polarize to a T helper (T_H)1-like state. Such T_reg cells possess effector functions, such as the production of IFNγ, yet remain stable and potently limit virus-specific effector T cell function, CD8⁺ T cell proliferation and the formation of central memory T cells.

We show a crucial protective function for T follicular helper (T_FH)-like cells localized within granuloma-associated lymphoid tissue for Mycobacterium tuberculosis control in mouse models of tuberculosis. Antigen-specific B cells contribute to this strategic localization and the maturation of cytokine-producing T_FH-like cells.

The adipose tissue is rich in immune cells. In this Review, the authors cover adipose tissue myeloid cells and how they control and respond to inflammation and pathology.

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.

When an interstitial macrophage niche is empty, classical monocytes can proliferate locally in a manner that is restricted by the transcription factor MAFB, before undergoing differentiation into distinct macrophage subsets. These findings reveal a new function of monocytes and highlight the complex regulation of proliferation and differentiation during macrophage development.

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.

Hidalgo and colleagues discuss general functional features of the neutrophil compartment that may be relevant in physiological scenarios such as specialization in naïve tissues, diversification and functional bias in inflammatory sites.

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.

Homozygous expression of MHC-II alleles that confer susceptibility to type 1 diabetes limits the efficiency of thymic negative selection and allows for CXCR6⁺ pathogenic clones to orchestrate the disease process. Expression of a second MHC-II allele decreases β-islet CD4⁺ T cell affinity, and limits CD8 cross-priming and diabetes risk without presenting the cognate MHC-II islet self-antigen.