Volume 27 Issue 2, February 2026

A comprehensive single-cell atlas now reveals eosinophil heterogeneity across several mouse tissues, linking distinct cellular states to tissue residency and lifespan, and offering insights into their context-dependent phenotypic and functional adaptations.

Distinct monocyte gene expression programs were identified in people with long COVID after mild-to-moderate COVID-19 versus severe acute COVID-19, providing evidence that immunological dysregulation after mild acute COVID-19 may be the result of distinct pathobiological pathways.

A newly identified, TGFβ-inducible decoy receptor for IL-17 family cytokines reveals a feedback mechanism that limits mucosal inflammation, linking epithelial and lymphoid cell responses through a common cytokine axis that controls IL-17-driven immunity.

Immune dysfunction and aberrant metabolic remodeling are hallmarks of critical illness including sepsis. Metabolic adaptation of CD4⁺ T cells is now shown to contribute to immunosuppression and poor clinical outcomes in critical illness.

Comparative single-cell transcriptomic analysis identifies clonally expanded tissue-resident CD8⁺ T cells within the leptomeninges of individuals with neurodegenerative diseases. The findings suggest that this brain border region represents an active immune niche that contributes to neurodegeneration with disease-specific distinctions.

CD8⁺ T cells in tumors develop ‘metabolic exhaustion’ characterized by high levels of glycolysis and impaired fatty acid oxidation. Lipid peroxidation generates active aldehydes, which accumulate with exhaustion, further attenuate fatty acid oxidation and boost glycolysis, creating a vicious cycle. Blocking aldehydes restores metabolic balance and prevents T cell exhaustion.

FOXP3⁺ regulatory T (T_reg) cells are pivotal for peripheral tolerance and immune suppression. We show that the skin-derived cytokine TSLP promotes GATA3-expressing effector T_reg cells through a specific migratory DC2 subtype derived from transitional dendritic cells whose function requires OX40L, identifying a previously unrecognized tolerogenic axis across contexts of inflammation and cancer.

Single-cell transcriptional profiling of thymic dendritic cells (DCs) from mice in which distinct stages of T cell development were blocked shows that thymocyte subsets support DC homeostasis and activation. CD8 single-positive thymocytes indirectly promote interferon responses in DCs, whereas CD4 single-positive thymocytes engage in cognate interactions with cDC1s, driving CD40 signaling and activation required for central tolerance.

Here the authors show that PARP inhibition activates SIRT-1–FOXO1 signaling to drive transcriptional and metabolic reprogramming of CD8⁺ T cells into central memory T cells with superior recall capacity and efficacy in adoptive therapy.

Li and colleagues describe a monocyte-specific transcriptional state along with a persistent elevation of inflammatory markers specifically found in individuals with long COVID who had mild-to-moderate disease during acute SARS-CoV-2 infection.

Phosphorylation-dephosphorylation and ubiquitination tune TCR signaling to avoid self-reactivity. Kim and colleagues show that acetylation also modulates TCR signaling.

Qian and colleagues show that IL-17REL functions as a decoy receptor to suppress the effects of IL-17 family cytokines and reduce intestinal inflammation.

Rathmell and colleagues show that metabolic reprograming of regulatory T cells is associated with severity of critical illness in patients with and without sepsis.

Differentiating DCs express ALDH1A2, which produces retinoic acid and suppresses DC activity. Blocking this pathway with a new inhibitor, KyA33, enhances immune responses and boosts the effectiveness of DC cancer vaccines in mouse models.

Dendritic cells (DCs) are required to establish thymic central tolerance. Here Srinivasan et al. use single-cell transcriptomics to define thymic conventional dendritic cell (cDC) subsets and find that CD8⁺ single-positive thymocytes modulate the thymus environment to regulate plasmacytoid DC and cDC2 homeostasis and interferon signatures in DCs, while CD4⁺ single-positive thymocytes regulate cDC1 activation via cognate and CD40L–CD40 interactions.

Here the authors show a feedback loop between active aldehydes and fatty acid oxidation that can reprogram T cell metabolism to promote exhaustion thereby limiting antitumor T cell immunity.

The authors show how Vγ1⁺ γδ T cells produce IL-4 to drive early CD8⁺ T cell and dendritic cell responses to malaria infection in mice.

Bohlen and colleagues report that the E3 ubiquitin ligase CBL is necessary for the development, tolerance and activation of B cells in humans, unlike in mice where CBL deficiency results in loss of T cells.

Elyaman and colleagues performed comparative single-cell transcriptomic and TCR repertoire analyses on T cells obtained from human cadaver brain and leptomeningeal tissues from individuals diagnosed with neurodegenerative disease.

Here the authors perform longitudinal sampling of lymphoid organs along with fate mapping and matched single-cell RNA sequencing and TCR sequencing to define the developmental dynamics of follicular regulatory T (T_FR) cells. They find that T_FR cells undergo clonal expansion and progressive differentiation in a process that requires follicular helper T cells.

Recent work has revealed that dendritic cells (DCs) are more heterogeneous than previously thought, yet the functional roles of these newly described DC subsets remain unclear. Here, Li et al. find that in mice, TSLP from keratinocytes activates transitional DC-derived DC2 to promote GATA3⁺ regulatory T cells and mediate immunosuppression during inflammation and cancer.

In this Resource paper the authors provide a multiomic single-cell atlas of mouse eosinophil heterogeneity across various organs and use fate-mapping methods to look at the dynamics of residency.