Intestinal Foxl1+ cell-derived CXCL12 maintains epithelial homeostasis by modulating cellular metabolism.

Several mesenchymal cell populations are known to regulate intestinal stem cell (ISC) self-renewal and differentiation. However, the influences of signaling mediators derived from mesenchymal cells other than ISC niche factors on epithelial homeostasis remain poorly understood. Here, we show that host and microbial metabolites, such as taurine and GABA, act on PDGFRαhigh Foxl1high sub-epithelial mesenchymal cells to regulate their transcription.

Blood DNA virome associates with autoimmune diseases and COVID-19.

Aberrant immune responses to viral pathogens contribute to pathogenesis, but our understanding of pathological immune responses caused by viruses within the human virome, especially at a population scale, remains limited. We analyzed whole-genome sequencing datasets of 6,321 Japanese individuals, including patients with autoimmune diseases (psoriasis vulgaris, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), pulmonary alveolar proteinosis (PAP) or multiple sclerosis) and coronavirus disease 2019 (COVID-19), or healthy controls. We systematically quantified two constituents of the blood DNA virome, endogenous HHV-6 (eHHV-6) and anellovirus.

Downregulation of semaphorin 4A in keratinocytes reflects the features of non-lesional psoriasis.

Psoriasis is a multifactorial disorder mediated by IL-17-producing T cells, involving immune cells and skin-constituting cells. Semaphorin 4A (Sema4A), an immune semaphorin, is known to take part in T helper type 1/17 differentiation and activation. However, Sema4A is also crucial for maintaining peripheral tissue homeostasis and its involvement in skin remains unknown.

CAR-NK cells derived from cord blood originate mainly from CD56CD7CD34HLA-DRLin NK progenitor cells.

Cord blood (CB)-derived chimeric antigen receptor (CAR)-natural killer (NK) cells targeting CD19 have been shown to be effective against B cell malignancies. While human CD56 NK cells can be expanded , NK cells can also be differentiated from hematopoietic progenitor cells. It is still unclear whether CAR-NK cells originate from mature NK cells or NK progenitor cells in CB.

The immune memory of innate immune systems.

Immune memory has long been considered a function specific to adaptive immune systems; however, adaptive immune memory alone has not fully explained the mechanism by which vaccines exert their protective effects against non-target pathogens. Recently, trained immunity, in which human monocytes vaccinated with bacillus Calmette-Guérin become highly responsive to pathogens other than Mycobacterium tuberculosis, has been reported. However, a phenomenon called endotoxin tolerance is also known, in which monocyte responsiveness is attenuated after the first lipopolysaccharide stimulation.

Increased angiopoietin-1 improves nailfold capillary morphology in patients with systemic sclerosis.

Objective: Raynaud's phenomenon is a common symptom of systemic sclerosis. We previously reported that elbow heating increases angiopoietin-1 in the fingertips and alleviates Raynaud's phenomenon. Angiopoietin-1 levels decrease in patients with systemic sclerosis with severe capillary damage.

Spontaneous high clonal expansion of Wilms' tumor gene 1-specific cytotoxic T-lymphocytes in patients with Wilms' tumor gene 1-expressing solid tumor.

Wilms' tumor protein 1 (WT1)-targeted immunotherapy has been used in patients with leukemia and solid tumors. However, the spontaneous WT1-specific immune response before WT1 peptide vaccination in patients with WT1-expressing tumors (PTs) remains unclear. Therefore, we investigated whether WT1-specific cytotoxic CD8 T-lymphocytes (CTLs) are clonally expanded in the peripheral blood outside of tumor sites.

The pyruvate-GPR31 axis promotes transepithelial dendrite formation in human intestinal dendritic cells.

The intestinal lumen is rich in gut microbial metabolites that serve as signaling molecules for gut immune cells. G-protein-coupled receptors (GPCRs) sense metabolites and can act as key mediators that translate gut luminal signals into host immune responses. However, the impacts of gut microbe-GPCR interactions on human physiology have not been fully elucidated.

Peripheral and central regulation of neuro-immune crosstalk.

The neural and immune systems sense and respond to external stimuli to maintain tissue homeostasis. These systems do not function independently but rather interact with each other to effectively exert biological actions and prevent disease pathogenesis, such as metabolic, inflammatory, and infectious disorders. Mutual communication between these systems is also affected by tissue niche-specific signals that reflect the tissue environment.

Proteomics of blood extracellular vesicles in inflammatory respiratory diseases for biomarker discovery and new insights into pathophysiology.

Background: Inflammatory respiratory diseases, such as interstitial lung disease (ILD), bronchial asthma (BA), chronic obstructive pulmonary disease (COPD), and respiratory infections, remain significant global health concerns owing to their chronic and severe nature. Emerging as a valuable resource, blood extracellular vesicles (EVs) offer insights into disease pathophysiology and biomarker discovery in these conditions.

Main Body: This review explores the advancements in blood EV proteomics for inflammatory respiratory diseases, highlighting their potential as non-invasive diagnostic and prognostic tools.

Safety, pharmacokinetics, biomarker response and efficacy of E6742: a dual antagonist of Toll-like receptors 7 and 8, in a first in patient, randomised, double-blind, phase I/II study in systemic lupus erythematosus.

Objectives: To evaluate the safety, tolerability, pharmacokinetics (PK), biomarker response and efficacy of E6742 in a phase I/II study in patients with systemic lupus erythematosus (SLE).

Methods: Two sequential cohorts of patients with SLE were enrolled and randomised to 12 weeks of two times per day treatment with E6742 (100 or 200 mg; n=8 or 9) or placebo (n=9). The primary endpoint was safety, the secondary endpoints were PK and interferon gene signature (IGS), and the exploratory endpoints were efficacy and biomarker.

Clonal landscape of autoantibody-secreting plasmablasts in COVID-19 patients.

Whereas severe COVID-19 is often associated with elevated autoantibody titers, the underlying mechanism behind their generation has remained unclear. Here we report clonal composition and diversity of autoantibodies in humoral response to SARS-CoV-2. Immunoglobulin repertoire analysis and characterization of plasmablast-derived monoclonal antibodies uncovered clonal expansion of plasmablasts producing cardiolipin (CL)-reactive autoantibodies.

Pathological mechanisms and novel drug targets in fibrotic interstitial lung disease.

Background: Interstitial lung diseases (ILDs) are a diverse group of conditions characterized by inflammation and fibrosis in the lung. In some patients with ILD, a progressive fibrotic phenotype develops, which is associated with an irreversible decline in lung function and a poor prognosis.

Main Body: The pathological mechanisms that underlie this process culminate in fibroblast activation, proliferation, and differentiation into myofibroblasts, which deposit extracellular matrix proteins and result in fibrosis.

Semaphorin 6D tunes amygdalar circuits for emotional, metabolic, and inflammatory outputs.

Regulated neural-metabolic-inflammatory responses are essential for maintaining physiological homeostasis. However, the molecular machinery that coordinates neural, metabolic, and inflammatory responses is largely unknown. Here, we show that semaphorin 6D (SEMA6D) coordinates anxiogenic, metabolic, and inflammatory outputs from the amygdala by maintaining synaptic homeostasis.