Multimodal transcriptomics reveal neurogenic aging trajectories and age-related regional inflammation in the dentate gyrus.

The mammalian dentate gyrus (DG) is involved in certain forms of learning and memory, and DG dysfunction has been implicated in age-related diseases. Although neurogenic potential is maintained throughout life in the DG as neural stem cells (NSCs) continue to generate new neurons, neurogenesis decreases with advancing age, with implications for age-related cognitive decline and disease. In this study, we used single-cell RNA sequencing to characterize transcriptomic signatures of neurogenic cells and their surrounding DG niche, identifying molecular changes associated with neurogenic aging from the activation of quiescent NSCs to the maturation of fate-committed progeny.

Social and Cognitive Skills (SCOPE)-a generic model for multi-professional work and education in healthcare.

In this article, we present a generic model for social and cognitive skills that can be used in work and (simulation-based) education in healthcare. We combined existing non-technical skills tools into a tool that we call SCOPE. SCOPE is a model that comprises the three social categories of "teamwork", "leading", and "task management" as well as the two cognitive categories of "situation awareness" and "decision making".

The Significant Role of PA28αβ in CD8 T Cell-Mediated Graft Rejection Contrasts with Its Negligible Impact on the Generation of MHC-I Ligands.

The proteasome generates the majority of peptides presented on MHC class I molecules. The cleavage pattern of the proteasome has been shown to be changed via the proteasome activator (PA)28 alpha beta (PA28αβ). In particular, several immunogenic peptides have been reported to be PA28αβ-dependent.

Twin study dissects CXCR3 memory B cells as non-heritable feature in multiple sclerosis.

Background: In multiple sclerosis (MS), B cells are considered main triggers of the disease, likely as the result of complex interaction between genetic and environmental risk factors. Studies on monozygotic twins discordant for MS offer a unique way to reduce this complexity and reveal discrepant subsets.

Methods: In this study, we analyzed B cell subsets in blood samples of monozygotic twins with and without MS using publicly available data.

B cell depletion attenuates CD27 signaling of T helper cells in multiple sclerosis.

Multiple sclerosis is a chronic inflammatory disease of the central nervous system. Whereas T cells are likely the main drivers of disease development, the striking efficacy of B cell-depleting therapies (BCDTs) underscore B cells' involvement in disease progression. How B cells contribute to multiple sclerosis (MS) pathogenesis-and consequently the precise mechanism of action of BCDTs-remains elusive.

IL-12 sensing in neurons induces neuroprotective CNS tissue adaptation and attenuates neuroinflammation in mice.

Interleukin-12 (IL-12) is a potent driver of type 1 immunity. Paradoxically, in autoimmune conditions, including of the CNS, IL-12 reduces inflammation. The underlying mechanism behind these opposing properties and the involved cellular players remain elusive.

High-dimensional analysis of 16 SARS-CoV-2 vaccine combinations reveals lymphocyte signatures correlating with immunogenicity.

The range of vaccines developed against severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) provides a unique opportunity to study immunization across different platforms. In a single-center cohort, we analyzed the humoral and cellular immune compartments following five coronavirus disease 2019 (COVID-19) vaccines spanning three technologies (adenoviral, mRNA and inactivated virus) administered in 16 combinations. For adenoviral and inactivated-virus vaccines, heterologous combinations were generally more immunogenic compared to homologous regimens.

Antibodies Produced by CLL Phenotype B Cells in Patients With Myasthenia Gravis Are Not Directed Against Neuromuscular Endplates.

Background And Objectives: Myasthenia gravis (MG) can in rare cases be an autoimmune phenomenon associated with hematologic malignancies such as chronic lymphocytic leukemia (CLL). It is unclear whether in patients with MG and CLL, the leukemic B cells are the ones directly driving the autoimmune response against neuromuscular endplates.

Methods: We identified patients with acetylcholine receptor antibody-positive (AChR) MG and CLL or monoclonal B-cell lymphocytosis (MBL), a precursor to CLL, and described their clinical features, including treatment responses.

The CNS mononuclear phagocyte system in health and disease.

CNS-resident macrophages-including parenchymal microglia and border-associated macrophages (BAMs)-contribute to neuronal development and health, vascularization, and tissue integrity at steady state. Border-patrolling mononuclear phagocytes such as dendritic cells and monocytes confer important immune functions to the CNS, protecting it from pathogenic threats including aberrant cell growth and brain malignancies. Even though we have learned much about the contribution of lymphocytes to CNS pathologies, a better understanding of differential roles of tissue-resident and -invading phagocytes is slowly emerging.

Azathioprine therapy induces selective NK cell depletion and IFN-γ deficiency predisposing to herpesvirus reactivation.

Background: Azathioprine is a widely prescribed drug for patients with chronic inflammatory diseases such as myasthenia gravis or organ transplant recipients. Azathioprine exerts immunosuppressive effects by inhibiting intracellular purine synthesis and reducing the numbers of circulating B and T lymphocytes. Case reports indicate increased risk for serious infections that can occur despite regular measurements of lymphocyte counts during azathioprine therapy.

Twin study reveals non-heritable immune perturbations in multiple sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system underpinned by partially understood genetic risk factors and environmental triggers and their undefined interactions. Here we investigated the peripheral immune signatures of 61 monozygotic twin pairs discordant for MS to dissect the influence of genetic predisposition and environmental factors. Using complementary multimodal high-throughput and high-dimensional single-cell technologies in conjunction with data-driven computational tools, we identified an inflammatory shift in a monocyte cluster of twins with MS, coupled with the emergence of a population of IL-2 hyper-responsive transitional naive helper T cells as MS-related immune alterations.

Single-cell profiling of immune system alterations in lymphoid, barrier and solid tissues in aged mice.

Aging exerts profound and paradoxical effects on the immune system, at once impairing proliferation, cytotoxicity and phagocytosis, and inducing chronic inflammation. Previous studies have focused on individual tissues or cell types, while a comprehensive multisystem study of tissue-resident and circulating immune populations during aging is lacking. Here we reveal an atlas of age-related changes in the abundance and phenotype of immune cell populations across 12 mouse tissues.

Single-cell profiling of myasthenia gravis identifies a pathogenic T cell signature.

Myasthenia gravis (MG) is an autoimmune disease characterized by impaired neuromuscular signaling due to autoantibodies targeting the acetylcholine receptor. Although its auto-antigens and effector mechanisms are well defined, the cellular and molecular drivers underpinning MG remain elusive. Here, we employed high-dimensional single-cell mass and spectral cytometry of blood and thymus samples from MG patients in combination with supervised and unsupervised machine-learning tools to gain insight into the immune dysregulation underlying MG.

The dural sinus hub: more than just a brain drain.

Recent findings of an active neuroimmune exchange at brain border regions have challenged the concept of the immune-privileged central nervous system. The study by Rustenhoven et al. in this issue of Cell shows that dural sinuses serve as a conduit for brain-derived antigens to interact with the immune system, allowing in situ immune surveillance.

Keratinocytes control skin immune homeostasis through de novo-synthesized glucocorticoids.

Glucocorticoids (GC), synthesized by the 11β-hydroxylase (Cyp11b1), control excessive inflammation through immunosuppressive actions. The skin was proposed to regulate homeostasis by autonomous GC production in keratinocytes. However, their immunosuppressive capacity and clinical relevance remain unexplored.

Druggability Assessment for Selected Serine Proteases in a Pharmaceutical Industry Setting.

Target druggability assessment is an integral part of the early target characterization and selection process in pharmaceutical industry. Here, we investigate a set of five different serine proteases from the blood coagulation cascade. The aim of this study is twofold.

CYBB/NOX2 in conventional DCs controls T cell encephalitogenicity during neuroinflammation.

Whereas central nervous system (CNS) homeostasis is highly dependent on tissue surveillance by immune cells, dysregulated entry of leukocytes during autoimmune neuroinflammation causes severe immunopathology and neurological deficits. To invade the CNS parenchyma, encephalitogenic T helper (T) cells must encounter their cognate antigen(s) presented by local major histocompatibility complex (MHC) class II-expressing antigen-presenting cells (APCs). The precise mechanisms by which CNS-associated APCs facilitate autoimmune T cell reactivation remain largely unknown.

The CNS Immune Landscape from the Viewpoint of a T Cell.

Neuro-immune interactions are not only vital for the control of neurotropic pathogens, but also appear to influence brain development and homeostasis. During immune surveillance, T cells can patrol the CNS-associated border regions to sense pathogenic alterations. While access to the CNS parenchyma is restricted in the steady state, various disease processes can initiate parenchymal T cell CNS invasion.

Conventional DCs sample and present myelin antigens in the healthy CNS and allow parenchymal T cell entry to initiate neuroinflammation.

The central nervous system (CNS) is under close surveillance by immune cells, which mediate tissue homeostasis, protection, and repair. Conversely, in neuroinflammation, dysregulated leukocyte invasion into the CNS leads to immunopathology and neurological disability. To invade the brain parenchyma, autoimmune encephalitogenic T helper (T) cells must encounter their cognate antigens (Ags) presented via local Ag-presenting cells (APCs).

ATG-dependent phagocytosis in dendritic cells drives myelin-specific CD4 T cell pathogenicity during CNS inflammation.

Although reactivation and accumulation of autoreactive CD4 T cells within the CNS are considered to play a key role in the pathogenesis of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), the mechanisms of how these cells recognize their target organ and induce sustained inflammation are incompletely understood. Here, we report that mice with conditional deletion of the essential autophagy protein ATG5 in classical dendritic cells (DCs), which are present at low frequencies in the nondiseased CNS, are completely resistant to EAE development following adoptive transfer of myelin-specific T cells and show substantially reduced in situ CD4 T cell accumulation during the effector phase of the disease. Endogenous myelin peptide presentation to CD4 T cells following phagocytosis of injured, phosphatidylserine-exposing oligodendroglial cells is abrogated in the absence of ATG5.

Diversity and bioactivities of nostocacean cyanobacteria isolated from paddy soil in Vietnam.

Nostocacean cyanobacteria are one of the important components of paddy fields due to their ability to fix atmospheric nitrogen and supply phytohormones for crop growth. In this study, 13 Nostoc strains isolated from paddy soils in Vietnam were classified using a polyphasic approach. The results showed a high diversity of the isolated strains that represented seven morphotypes corresponding to five genotypes, with 16S rRNA gene sequence similarity values ranging between 94.