The Human Microglia Atlas (HuMicA) unravels changes in disease-associated microglia subsets across neurodegenerative conditions.

Dysregulated microglia activation, leading to neuroinflammation, is crucial in neurodegenerative disease development and progression. We constructed an atlas of human brain immune cells by integrating nineteen single-nucleus RNA-seq and single-cell RNA-seq datasets from multiple neurodegenerative conditions, comprising 241 samples from patients with Alzheimer's disease, autism spectrum disorder, epilepsy, multiple sclerosis, Lewy body diseases, COVID-19, and healthy controls. The integrated Human Microglia Atlas (HuMicA) included 90,716 nuclei/cells and revealed nine populations distributed across all conditions.

COVID-19 progression and convalescence in common variable immunodeficiency patients show dysregulated adaptive immune responses and persistent type I interferon and inflammasome activation.

Common variable immunodeficiency (CVID) is the most prevalent primary immunodeficiency, marked by hypogammaglobulinemia, poor antibody responses, and increased infection susceptibility. The COVID-19 pandemic provided a unique opportunity to study the effects of prolonged viral infections on the immune responses of CVID patients. Here we use single-cell RNA-seq and spectral flow cytometry of peripheral blood samples before, during, and after SARS-CoV-2 infection showing that COVID-19 CVID patients display a persistent type I interferon signature at convalescence across immune compartments.

NF-κB and TET2 promote macrophage reprogramming in hypoxia that overrides the immunosuppressive effects of the tumor microenvironment.

Macrophages orchestrate tissue homeostasis and immunity. In the tumor microenvironment (TME), macrophage presence is largely associated with poor prognosis because of their reprogramming into immunosuppressive cells. We investigated the effects of hypoxia, a TME-associated feature, on the functional, epigenetic, and transcriptional reprogramming of macrophages and found that hypoxia boosts their immunogenicity.

Tinostamustine (EDO-S101), an Alkylating Deacetylase Inhibitor, Enhances the Efficacy of Daratumumab in Multiple Myeloma by Upregulation of CD38 and NKG2D Ligands.

Multiple myeloma is a malignancy characterized by the accumulation of malignant plasma cells in bone marrow and the production of monoclonal immunoglobulin. A hallmark of cancer is the evasion of immune surveillance. Histone deacetylase inhibitors have been shown to promote the expression of silenced molecules and hold potential to increase the anti-MM efficacy of immunotherapy.

Disease activity drives divergent epigenetic and transcriptomic reprogramming of monocyte subpopulations in systemic lupus erythematosus.

Objectives: Systemic lupus erythematosus (SLE) is characterised by systemic inflammation involving various immune cell types. Monocytes, pivotal in promoting and regulating inflammation in SLE, differentiate from classic monocytes into intermediate and non-classic monocytes, assuming diverse roles and changing their proportions in inflammation. In this study, we investigated the epigenetic and transcriptomic profiles of these and novel monocyte subsets in SLE in relation to activity and progression.