Clonal relationships between Tph and Tfh cells in patients with SLE and in murine lupus.

Pathologic T cell-B cell interactions drive disease in systemic lupus erythematosus (SLE). The T cells that activate B cell responses include T peripheral helper (Tph) and T follicular helper (Tfh) cells, yet the developmental and clonal relationships between these B cell-helper T cell populations are unclear. Here we use T cell receptor (TCR) profiling to demonstrate clonal overlap between Tph and Tfh cells in the circulation of patients with SLE.

Apoptotic vesicles rescue impaired mesenchymal stem cells and their therapeutic capacity for osteoporosis by restoring miR-145a-5p deficiency.

Apoptotic vesicles (apoVs) play a vital role in various pathological conditions; however, we have yet to fully understand their precise biological effects in rescuing impaired mesenchymal stem cells (MSCs) and regulating tissue homeostasis. Here, we proved that systemic infusion of bone marrow MSCs derived from wild-type (WT) mice effectively improved the osteopenia phenotype and hyperimmune state in ovariectomized (OVX) mice. Importantly, the WT MSCs rescued the impairment of OVX MSCs both and , whereas OVX MSCs did not show the same efficacy.

A PD-1CD4 T Cell Population With a Cytotoxic Phenotype is Associated With Interstitial Lung Disease in Systemic Sclerosis.

Objective: T cells contribute to tissue injury in systemic sclerosis (SSc), yet the specific T cell subsets expanded in patients with SSc remain incompletely defined. Here we evaluated specific phenotypes and functions of peripheral helper T (Tph) and follicular helper T (Tfh) cells, which have been implicated in autoantibody production, and assessed their associations with clinical features in a well-characterized cohort of patients with SSc.

Methods: Mass cytometry of T cells from peripheral blood mononuclear cells of patients with SSc and controls were evaluated using t-distributed stochastic neighbor embedding visualization, biaxial gating, and marker expression levels.

Fibroblast expression of neurotransmitter receptor HTR2A associates with inflammation in rheumatoid arthritis joint.

The study of neuroimmune crosstalk and the involvement of neurotransmitters in inflammation and bone health has illustrated their significance in joint-related conditions. One important mode of cell-to-cell communication in the synovial fluid (SF) is through extracellular vesicles (EVs) carrying microRNAs (miRNAs). The role of neurotransmitter receptors in the pathogenesis of inflammatory joint diseases, and whether there are specific miRNAs regulating differentially expressed HTR2A, contributing to the inflammatory processes and bone metabolism is unclear.

Anti-synthetase syndrome is associated with a higher risk of hospitalization among patients with idiopathic inflammatory myopathy and COVID-19.

Background: Data with fine granularity about COVID-19-related outcomes and risk factors were still limited in the idiopathic inflammatory myopathies (IIMs) population. This study aimed to investigate clinical factors associated with hospitalized and severe COVID-19 in patients with IIMs, particularly those gauged by myositis-specific antibodies.

Methods: This retrospective cohort study was conducted in the Renji IIM cohort in Shanghai, China, under an upsurge of SARS-CoV-2 omicron variant infections from December 2022 to January 2023.

Apoptotic Vesicular Metabolism Contributes to Organelle Assembly and Safeguards Liver Homeostasis and Regeneration.

Background & Aims: Apoptosis generates plenty of membrane-bound nanovesicles, the apoptotic vesicles (apoVs), which show promise for biomedical applications. The liver serves as a significant organ for apoptotic material removal. Whether and how the liver metabolizes apoptotic vesicular products and contributes to liver health and disease is unrecognized.

Clonally expanded CD38 cytotoxic CD8 T cells define the T cell infiltrate in checkpoint inhibitor-associated arthritis.

Immune checkpoint inhibitor (ICI) therapies used to treat cancer, such as anti-PD-1 antibodies, can induce autoimmune conditions in some individuals. The T cell mechanisms mediating such iatrogenic autoimmunity and their overlap with spontaneous autoimmune diseases remain unclear. Here, we compared T cells from the joints of 20 patients with an inflammatory arthritis induced by ICI therapy (ICI-arthritis) with two archetypal autoimmune arthritides, rheumatoid arthritis (RA) and psoriatic arthritis (PsA).

Apoptotic vesicles ameliorate lupus and arthritis via phosphatidylserine-mediated modulation of T cell receptor signaling.

Mesenchymal stem cells (MSCs) influence T cells in health, disease and therapy through messengers of intercellular communication including extracellular vesicles (EVs). Apoptosis is a mode of cell death that tends to promote immune tolerance, and a large number of apoptotic vesicles (apoVs) are generated from MSCs during apoptosis. In an effort to characterize these apoVs and explore their immunomodulatory potential, here we show that after replenishing them systemically, the apoV deficiency in mutant mice and pathological lymphoproliferation were rescued, leading to the amelioration of inflammation and lupus activity.

Two Distinct Immune Cell Signatures Predict the Clinical Outcomes in Patients With Amyopathic Dermatomyositis With Interstitial Lung Disease.

Objective: Amyopathic dermatomyositis (ADM) is a heterogeneous and life-threatening autoimmune disease with a high mortality rate. In particular, anti-melanoma differentiation-associated protein 5 antibody-positive patients are at a high risk of developing rapidly progressive interstitial lung disease (RPILD). This study was undertaken to identify immunologic signatures among patients who have ADM with ILD (ADM-ILD) and to discover the biomarkers predicting prognosis.

Granzyme K CD8 T cells form a core population in inflamed human tissue.

T cell-derived pro-inflammatory cytokines are a major driver of rheumatoid arthritis (RA) pathogenesis. Although these cytokines have traditionally been attributed to CD4 T cells, we have found that CD8 T cells are notably abundant in synovium and make more interferon (IFN)-γ and nearly as much tumor necrosis factor (TNF) as their CD4 T cell counterparts. Furthermore, using unbiased high-dimensional single-cell RNA-seq and flow cytometric data, we found that the vast majority of synovial tissue and synovial fluid CD8 T cells belong to an effector CD8 T cell population characterized by high expression of granzyme K (GzmK) and low expression of granzyme B (GzmB) and perforin.

Mesenchymal stem cells empower T cells in the lymph nodes via MCP-1/PD-L1 axis.

Mesenchymal stem cells (MSCs) are a type of immunosuppressive stromal cell found in multiple tissues and organs. However, whether MSCs possess immunosupportive characteristics remains unclear. In this study, we showed that the lymph nodes contain immunosupportive MSCs.

Identification of T Peripheral Helper (Tph) Cells.

T peripheral helper (Tph) cells represent a T cell population that stimulates B cell responses within peripheral tissues. Like T follicular helper (Tfh) cells, PD-1 CXCR5 CD4 Tph cells produce IL-21 and CXCL13, yet these cells differ from Tfh cells in expression of both transcription factors and chemokine receptors. Originally identified in rheumatoid arthritis synovium, Tph cells are expanded in multiple autoimmune diseases.

Mechanical force-driven TNFα endocytosis governs stem cell homeostasis.

Mesenchymal stem cells (MSCs) closely interact with the immune system, and they are known to secrete inflammatory cytokines in response to stress stimuli. The biological function of MSC-derived inflammatory cytokines remains elusive. Here, we reveal that even under physiological conditions, MSCs produce and release a low level of tumor necrosis factor alpha (TNFα), which is unexpectedly required for preserving the self-renewal and differentiation of MSCs via autocrine/paracrine signaling.

Autophagy controls mesenchymal stem cell therapy in psychological stress colitis mice.

Mesenchymal stem cell transplantation (MSCT) has been applied to treat a variety of autoimmune and inflammatory diseases. Psychosocial stress can aggravate disease progression in chronic inflammatory patients. Whether psychological stress affects MSCT is largely unknown.

Circulating apoptotic bodies maintain mesenchymal stem cell homeostasis and ameliorate osteopenia via transferring multiple cellular factors.

In the human body, 50-70 billion cells die every day, resulting in the generation of a large number of apoptotic bodies. However, the detailed biological role of apoptotic bodies in regulating tissue homeostasis remains unclear. In this study, we used Fas-deficient MRL/lpr and Caspase 3 mice to show that reduction of apoptotic body formation significantly impaired the self-renewal and osteo-/adipo-genic differentiation of bone marrow mesenchymal stem cells (MSCs).