Update: Induction of Inflammatory Bowel Disease in Immunodeficient Mice by Injection of Naïve CD4 T cells (T Cell Transfer Model of Colitis).

The intestinal inflammation induced by injection of naïve CD4 T cells into lymphocyte-deficient hosts (more commonly known as the T cell transfer model of colitis) shares many features of idiopathic inflammatory bowel disease (IBD) in humans, such as epithelial cell hyperplasia, crypt abscess formation, and dense lamina propria lymphocyte infiltration. As such, it provides a useful tool for studying mucosal immune regulation as it relates to the pathogenesis and treatment of IBD in humans. In the IBD model described here, colitis is induced in Rag (recombination-activating gene)-deficient mice by reconstitution of these mice with naïve CD4CD45RB T cells through adoptive T cell transfer.

The future of immunology: a Lofoten perspective.

This Future Challenges article summarizes views on future directions in immunological research presented at round-table discussions at the 4th Immunology workshop in the Lofoten Islands in Norway, held in August 2023, and subsequent responses to surveys sent to meeting participants. It also summarizes some of the conversations around the responsibility of scientists to communicate with the non-science community, and the approaches that we may use to meet this obligation.

isolateR: an R package for generating microbial libraries from Sanger sequencing data.

Motivation: Sanger sequencing of taxonomic marker genes (e.g. 16S/18S/ITS/rpoB/cpn60) represents the leading method for identifying a wide range of microorganisms including bacteria, archaea, and fungi.

Dynamic Human Gut Microbiome and Immune Shifts During an Immersive Psychosocial Therapeutic Program.

Background: Depression is a leading cause of disability worldwide yet its underlying factors, particularly microbial associations, are poorly understood.

Methods: We examined the longitudinal interplay between the microbiome and immune system in the context of depression during an immersive psychosocial intervention. 142 multi-omics samples were collected from 52 well-characterized participants before, during, and three months after a nine-day inquiry-based stress reduction program.

Regulation of temporal cytokine production by co-stimulation receptors in TCR-T cells is lost in CAR-T cells.

CD8+ T cells contribute to immune responses by producing cytokines when their T-cell receptors (TCRs) recognise peptide antigens on major-histocompability-complex class I. However, excessive cytokine production can be harmful. For example, cytokine release syndrome is a common toxicity observed in treatments that activate T cells, including chimeric antigen receptor (CAR)-T-cell therapy.

Panpipes: a pipeline for multiomic single-cell and spatial transcriptomic data analysis.

Single-cell multiomic analysis of the epigenome, transcriptome, and proteome allows for comprehensive characterization of the molecular circuitry that underpins cell identity and state. However, the holistic interpretation of such datasets presents a challenge given a paucity of approaches for systematic, joint evaluation of different modalities. Here, we present Panpipes, a set of computational workflows designed to automate multimodal single-cell and spatial transcriptomic analyses by incorporating widely-used Python-based tools to perform quality control, preprocessing, integration, clustering, and reference mapping at scale.

Vesicle transport of matrix metalloproteinases.

Multicellular organisms consist of cells and extracellular matrix (ECM). ECM creates a cellular microenvironment, and cells locally degrade the ECM according to their cellular activity. A major group of enzymes that modify ECM belongs to matrix metalloproteinases (MMPs) and play major roles in various pathophysiological events.

TRPC3 signalling contributes to the biogenesis of extracellular vesicles.

Extracellular vesicles (EVs) contribute to a wide range of pathological processes including cancer progression, yet the molecular mechanisms underlying their biogenesis remain incompletely characterized. The development of tetraspanin-based pHluorin reporters has enabled the real-time analysis of EV release at the plasma membrane. Here, we employed CD81-pHluorin to investigate mechanisms of EV release in ovarian cancer (OC) cells and report a novel role for the Ca-permeable transient receptor potential (TRP) channel TRPC3 in EV-mediated communication.

History of tuberculosis disease is associated with genetic regulatory variation in Peruvians.

A quarter of humanity is estimated to have been exposed to Mycobacterium tuberculosis (Mtb) with a 5-10% risk of developing tuberculosis (TB) disease. Variability in responses to Mtb infection could be due to host or pathogen heterogeneity. Here, we focused on host genetic variation in a Peruvian population and its associations with gene regulation in monocyte-derived macrophages and dendritic cells (DCs).

Immunological synapse formation between T regulatory cells and cancer-associated fibroblasts promotes tumour development.

Cancer-associated fibroblasts (CAFs) have emerged as a dominant non-hematopoietic cell population in the tumour microenvironment, serving diverse functions in tumour progression. However, the mechanisms via which CAFs influence the anti-tumour immunity remain poorly understood. Here, using multiple tumour models and biopsies from cancer patients, we report that α-SMA CAFs can form immunological synapses with Foxp3 regulatory T cells (Tregs) in tumours.

Increased interleukin-26 in the peripheral joints of patients with axial spondyloarthritis and psoriatic arthritis, co-localizing with CD68-positive synoviocytes.

Objectives: levels are elevated in the blood and synovial fluid of patients with inflammatory arthritis. can be produced by Th17 cells and locally within joints by tissue-resident cells. induces osteoblast mineralization .

A general algorithm for consensus 3D cell segmentation from 2D segmented stacks.

Cell segmentation is the fundamental task. Only by segmenting, can we define the quantitative spatial unit for collecting measurements to draw biological conclusions. Deep learning has revolutionized 2D cell segmentation, enabling generalized solutions across cell types and imaging modalities.

Soft Synthetic Cells with Mobile Membrane Ligands for Ex Vivo Expansion of Therapy-Relevant T Cell Phenotypes.

The expansion of T cells ex vivo is crucial for effective immunotherapy but currently limited by a lack of expansion approaches that closely mimic in vivo T cell activation. Taking inspiration from bottom-up synthetic biology, a new synthetic cell technology is introduced based on dispersed liquid-liquid phase-separated droplet-supported lipid bilayers (dsLBs) with tunable biochemical and biophysical characteristics, as artificial antigen presenting cells (aAPCs) for ex vivo T cell expansion. These findings obtained with the dsLB technology reveal three key insights: first, introducing laterally mobile stimulatory ligands on soft aAPCs promotes expansion of IL-4/IL-10 secreting regulatory CD8 T cells, with a PD-1 negative phenotype, less prone to immune suppression.

Dietary fibre supplementation enhances radiotherapy tumour control and alleviates intestinal radiation toxicity.

Background: Non-toxic approaches to enhance radiotherapy outcomes are beneficial, particularly in ageing populations. Based on preclinical findings showing that high-fibre diets sensitised bladder tumours to irradiation by modifying the gut microbiota, along with clinical evidence of prebiotics enhancing anti-cancer immunity, we hypothesised that dietary fibre and its gut microbiota modification can radiosensitise tumours via secretion of metabolites and/or immunomodulation. We investigated the efficacy of high-fibre diets combined with irradiation in immunoproficient C57BL/6 mice bearing bladder cancer flank allografts.

Blood RNA-sequencing across the continuum of ANA-positive autoimmunity reveals insights into initiating immunopathology.

Objective: Mechanisms underpinning clinical evolution to systemic lupus erythematosus (SLE) from preceding antinuclear antibodies (ANA) positivity are poorly understood. This study aimed to understand blood immune cell transcriptional signatures associated with subclinical ANA positivity, and progression or non-progression to SLE.

Methods: Bulk RNA-sequencing of peripheral blood mononuclear cells isolated at baseline from 35 ANA positive (ANA+) subjects with non-diagnostic symptoms was analysed using differential gene expression, weighted gene co-expression network analysis, deconvolution of cell subsets and functional enrichment analyses.

IL-23 past, present, and future: a roadmap to advancing IL-23 science and therapy.

Interleukin (IL)-23, an IL-12 cytokine family member, is a hierarchically dominant regulatory cytokine in a cluster of immune-mediated inflammatory diseases (IMIDs), including psoriasis, psoriatic arthritis, and inflammatory bowel disease. We review IL-23 biology, IL-23 signaling in IMIDs, and the effect of IL-23 inhibition in treating these diseases. We propose studies to advance IL-23 biology and unravel differences in response to anti-IL-23 therapy.

hadge: a comprehensive pipeline for donor deconvolution in single-cell studies.

Single-cell multiplexing techniques (cell hashing and genetic multiplexing) combine multiple samples, optimizing sample processing and reducing costs. Cell hashing conjugates antibody-tags or chemical-oligonucleotides to cell membranes, while genetic multiplexing allows to mix genetically diverse samples and relies on aggregation of RNA reads at known genomic coordinates. We develop hadge (hashing deconvolution combined with genotype information), a Nextflow pipeline that combines 12 methods to perform both hashing- and genotype-based deconvolution.

Regulation of pulmonary plasma cell responses during secondary infection with influenza virus.

During secondary infection with influenza virus, plasma cells (PCs) develop within the lung, providing a local source of antibodies. However, the site and mechanisms that regulate this process are poorly defined. Here, we show that while circulating memory B cells entered the lung during rechallenge and were activated within inducible bronchus-associated lymphoid tissues (iBALTs), resident memory B (BRM) cells responded earlier, and their activation occurred in a different niche: directly near infected alveoli.

Inflammation-based scores in patients with pheochromocytoma.

Background: Pheochromocytoma is associated with systemic inflammation, but the underlying mechanisms are unclear. Therefore, we investigated the relationship between plasma metanephrine levels and haematological parameters - as a surrogate of inflammation - in patients with pheochromocytoma and the influence of preoperative α-blockade treatment.

Design And Methods: We retrospectively studied 68 patients with pheochromocytoma who underwent adrenalectomy (median age 53 years, 64.