Specific immune response to and ability to control mycobacterial replication are not impaired in subjects with immune-mediated inflammatory disease and tuberculosis infection.

Background: Subjects with immune-mediated inflammatory diseases (IMID), such as rheumatoid arthritis, with tuberculosis infection (TBI), have a high probability of progressing to tuberculosis disease (TB). We aim to characterize the impact of IMID on the immune response to (Mtb) in patients with TBI and TB disease.

Methods: We enrolled TBI and TB patients with and without IMID.

Tissue-resident memory CD8 T cell diversity is spatiotemporally imprinted.

Tissue-resident memory CD8 T (T) cells provide protection from infection at barrier sites. In the small intestine, T cells are found in at least two distinct subpopulations: one with higher expression of effector molecules and another with greater memory potential. However, the origins of this diversity remain unknown.

The XCL1-XCR1 axis supports intestinal tissue residency and antitumor immunity.

Tissue-resident memory T cells (TRM) provide frontline protection against pathogens and emerging malignancies. Tumor-infiltrating lymphocytes (TIL) with TRM features are associated with improved clinical outcomes. However, the cellular interactions that program TRM differentiation and function are not well understood.

Evolution of SARS-CoV-2 T cell responses as a function of multiple COVID-19 boosters.

The long-term effects of repeated COVID-19 vaccinations on adaptive immunity remain incompletely understood. Here, we conducted a comprehensive three-year longitudinal study examining T cell and antibody responses in 78 vaccinated individuals without reported symptomatic infections. We observed distinct dynamics in Spike-specific humoral and cellular immune responses across multiple vaccine doses.

A Roadmap Towards the Identification and Validation of Conserved T Cell Epitope Regions in Viral Pathogen Families with Pandemic Potential.

The SARS-CoV-2 pandemic has highlighted the need for society, as a whole, to be prepared against potential pandemics caused by a variety of different viral families of concern. Here, we describe a roadmap towards the identification and validation of conserved T cell epitope regions from Viral Families of Pandemic Potential (VFPP). For each viral family, we select a prototype virus, the sequence of which could be utilized in epitope identification screens.

Reevaluating Anti-Inflammatory Therapy: Targeting Senescence to Balance Anti-Cancer Efficacy and Vascular Disease.

Modulating immune function is a critical strategy in cancer and atherosclerosis treatments. For cancer, boosting or maintaining the immune system is crucial to prevent tumor growth. However, in vascular disease, mitigating immune responses can decrease inflammation and slow atherosclerosis progression.

3D genomic features across >50 diverse cell types reveal insights into the genomic architecture of childhood obesity.

The prevalence of childhood obesity is increasing worldwide, along with the associated common comorbidities of type 2 diabetes and cardiovascular disease in later life. Motivated by evidence for a strong genetic component, our prior genome-wide association study (GWAS) efforts for childhood obesity revealed 19 independent signals for the trait; however, the mechanism of action of these loci remains to be elucidated. To molecularly characterize these childhood obesity loci, we sought to determine the underlying causal variants and the corresponding effector genes within diverse cellular contexts.

CFTR dictates monocyte adhesion by facilitating integrin clustering but not activation.

Monocytes are critical in controlling tissue infections and inflammation. Monocyte dysfunction contributes to the inflammatory pathogenesis of cystic fibrosis (CF) caused by CF transmembrane conductance regulator (CFTR) mutations, making CF a clinically relevant disease model for studying the contribution of monocytes to inflammation. Although CF monocytes exhibited adhesion defects, the precise mechanism is unclear.

nipalsMCIA: Flexible Multi-Block Dimensionality Reduction in R via Nonlinear Iterative Partial Least Squares.

Summary: With the increased reliance on multi-omics data for bulk and single cell analyses, the availability of robust approaches to perform unsupervised learning for clustering, visualization, and feature selection is imperative. We introduce nipalsMCIA, an implementation of multiple co-inertia analysis (MCIA) for joint dimensionality reduction that solves the objective function using an extension to Non-linear Iterative Partial Least Squares (NIPALS). We applied nipalsMCIA to both bulk and single cell datasets and observed significant speed-up over other implementations for data with a large sample size and/or feature dimension.

Multiomics dissection of human RAG deficiency reveals distinctive patterns of immune dysregulation but a common inflammatory signature.

Human recombination-activating gene (RAG) deficiency can manifest with distinct clinical and immunological phenotypes. By applying a multiomics approach to a large group of -mutated patients, we aimed at characterizing the immunopathology associated with each phenotype. Although defective T and B cell development is common to all phenotypes, patients with hypomorphic variants can generate T and B cells with signatures of immune dysregulation and produce autoantibodies to a broad range of self-antigens, including type I interferons.

Clinical and immunological outcomes after randomized trial of baked milk oral immunotherapy for milk allergy.

BACKGROUNDCow's milk (CM) allergy is the most common food allergy in young children. Treatment with oral immunotherapy (OIT) has shown efficacy, but high rates of adverse reactions. The aim of this study was to determine whether baked milk OIT (BMOIT) could reduce adverse reactions while still inducing desensitization, and to identify immunological correlates of successful BMOIT.

YAP-driven malignant reprogramming of oral epithelial stem cells at single cell resolution.

Tumor initiation represents the first step in tumorigenesis during which normal progenitor cells undergo cell fate transition to cancer. Capturing this process as it occurs in vivo, however, remains elusive. Here we employ spatiotemporally controlled oncogene activation and tumor suppressor inhibition together with multiomics to unveil the processes underlying oral epithelial progenitor cell reprogramming into tumor initiating cells at single cell resolution.

Integration of Stromal Cells and Hydrogel Below Epithelium Results in Optimal Barrier Properties of Small Intestine Organoid Models.

: The barrier properties of the human small intestine play a crucial role in regulating digestion, nutrient absorption and drug metabolism. Current in vitro organotypic models consist only of an epithelium, which does not take into account the possible role of stromal cells such as fibroblasts or the extracellular matrix (ECM) which could contribute to epithelial barrier properties. Therefore, the aim of this study was to determine whether these stromal cells or ECM were beneficial or detrimental to barrier function when incorporated into an organotypic human small intestine model.

Modulating the human gut microbiome and health markers through kombucha consumption: a controlled clinical study.

Fermented foods are becoming more popular due to their purported links to metabolic health and the gut microbiome. However, direct clinical evidence for the health claims is lacking. Here, we describe an eight-week clinical trial that explored the effects of a four-week kombucha supplement in healthy individuals consuming a Western diet, randomized into the kombucha (n = 16) or control (n = 8) group.

Unraveling the impact of SARS-CoV-2 mutations on immunity: insights from innate immune recognition to antibody and T cell responses.

Throughout the COVID-19 pandemic, the emergence of new viral variants has challenged public health efforts, often evading antibody responses generated by infections and vaccinations. This immune escape has led to waves of breakthrough infections, raising questions about the efficacy and durability of immune protection. Here we focus on the impact of SARS-CoV-2 Delta and Omicron spike mutations on ACE-2 receptor binding, protein stability, and immune response evasion.

Booster COVID-19 mRNA vaccination ameliorates impaired B-cell but not T-cell responses in older adults.

Age-associated differences in the effect of repetitive vaccination, particularly on memory T-cell and B-cell responses, remain unclear. While older adults (aged ≥65 years) exhibited enhanced IgG responses following COVID-19 mRNA booster vaccination, they produced fewer spike-specific circulating follicular helper T cells-1 than younger adults. Similarly, the cytotoxic CD8 T-cell response remained diminished with reduced PD-1 expression even after booster vaccination compared with that in younger adults, suggesting impaired memory T-cell activation in older adults.

The α glycolipid rules the NKT cell TCR.

In this issue of JEM, Hosono et al. (https://doi.org/10.

Targets of influenza human T-cell response are mostly conserved in H5N1.

Frequent recent spillovers of subtype H5N1 clade 2.3.4.

In-depth characterization of T cell responses with a combined Activation-Induced Marker (AIM) and Intracellular Cytokine Staining (ICS) assay.

Since T cells are key mediators in the adaptive immune system, evaluating antigen-specific T cell immune responses is pivotal to understanding immune function. Commonly used methods for measuring T cell responses include Activation-Induced Marker (AIM) assays and Intracellular Cytokine Staining (ICS). However, combining these approaches has rarely been reported.

Early antiviral CD4+ and CD8+ T cells are associated with upper airway clearance of SARS-CoV-2.

T cells are involved in protective immunity against numerous viral infections. Data regarding functional roles of human T cells in SARS-CoV-2 (SARS2) viral clearance in primary COVID-19 are limited. To address this knowledge gap, we assessed samples for associations between SARS2 upper respiratory tract viral RNA levels and early virus-specific adaptive immune responses for 95 unvaccinated clinical trial participants with acute primary COVID-19 aged 18-86 years old, approximately half of whom were considered at high risk for progression to severe COVID-19.

Co-immunization with spike and nucleocapsid based DNA vaccines for long-term protective immunity against SARS-CoV-2 Omicron.

The continuing evolution of SARS-CoV-2 variants challenges the durability of existing spike (S)-based COVID-19 vaccines. We hypothesized that vaccines composed of both S and nucleocapsid (N) antigens would increase the durability of protection by strengthening and broadening cellular immunity compared with S-based vaccines. To test this, we examined the immunogenicity and efficacy of wild-type SARS-CoV-2 S- and N-based DNA vaccines administered individually or together to K18-hACE2 mice.

Patterns and cofactors of polyfunctional mycobacteria-specific T cell response restoration following 6-month antiretroviral treatment in children living with HIV.

Background: Despite immune restoration after initiation of antiretroviral treatment (ART), the risk of tuberculosis (TB) persists in children living with HIV (CLHIV). We determined patterns of immune restoration of mycobacteria-specific T cells following ART in CLHIV.

Methods: CD4 and CD8 T cell activation and memory phenotype and functional profiles before and 6 months after ART were evaluated in peripheral blood mononuclear cells (PBMCs) from CLHIV enrolled in the PUSH study (NCT02063880) in Nairobi, Kenya.

PINK1 is a target of T cell responses in Parkinson's disease.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder. While there is no curative treatment, the immune system's involvement with autoimmune T cells that recognize the protein alpha-synuclein (α-syn) in a subset of individuals suggests new areas for therapeutic strategies. As not all patients with PD have T cells specific for α-syn, we explored additional autoantigenic targets of T cells in PD.