BAFF promotes follicular helper T cell development and germinal center formation through BR3 signal.

T follicular helper (Tfh) cells represent an important subset of CD4+ T cells that is crucial to the maturation and differentiation of B cells and the production of high-affinity antibodies. Because B cell activating-factor (BAFF), a vital B cell survival factor, is also crucial to B cell maturation and differentiation, we assessed the effects of BAFF on Tfh cell development and function. We demonstrated that deficiency of BAFF, but not of APRIL, markedly inhibited Tfh cell development, germinal center (GC) formation, and antigen-specific antibody production.

FTO-mediated RNA mA methylation regulates synovial aggression and inflammation in rheumatoid arthritis.

Fibroblast-like synoviocytes (FLS) plays an important role in synovial inflammation and joint damage in rheumatoid arthritis (RA). As the most abundant mRNA modification, N6-methyladenosine (mA) is involved in the development of various diseases; however, its role in RA remains to be defined. In this study, we reported the elevated expression of the mA demethylase fat mass and obesity-associated protein (FTO) in FLS and synovium from RA patients.

Lactylated Apolipoprotein C-II Induces Immunotherapy Resistance by Promoting Extracellular Lipolysis.

Mortality rates due to lung cancer are high worldwide. Although PD-1 and PD-L1 immune checkpoint inhibitors boost the survival of patients with non-small-cell lung cancer (NSCLC), resistance often arises. The Warburg Effect, which causes lactate build-up and potential lysine-lactylation (Kla), links immune dysfunction to tumor metabolism.

WTAP/YTHDF1-mediated mA modification amplifies IFN-γ-induced immunosuppressive properties of human MSCs.

Introduction: The immunosuppressive capacity of mesenchymal stem cells (MSCs) is dependent on the "license" of several pro-inflammatory factors to express immunosuppressive molecular profiles, which determines the therapeutic efficacy of MSCs in immune-mediated inflammatory diseases. Of those, interferon-γ (IFN-γ) is a key inducer for the expression of immunosuppressive molecular profiles; however, the mechanism underlying this effect is unknown.

Objectives: To elucidate the regulation mechanism and biological functions of N-methyladenosine (mA) modification in the immunosuppressive functions by the IFN-γ-licensing MSCs.

Gingival-derived mesenchymal stem cells alleviate allergic asthma inflammation via HGF in animal models.

Allergic asthma is a chronic non-communicable disease characterized by lung tissue inflammation. Current treatments can alleviate the clinical symptoms to some extent, but there is still no cure. Recently, the transplantation of mesenchymal stem cells (MSCs) has emerged as a potential approach for treating allergic asthma.

miRNA-148a-containing GMSC-derived EVs modulate Treg/Th17 balance via IKKB/NF-κB pathway and treat a rheumatoid arthritis model.

Mesenchymal stem cells (MSCs) have demonstrated potent immunomodulatory properties that have shown promise in the treatment of autoimmune diseases, including rheumatoid arthritis (RA). However, the inherent heterogeneity of MSCs triggered conflicting therapeutic outcomes, raising safety concerns and limiting their clinical application. This study aimed to investigate the potential of extracellular vesicles derived from human gingival mesenchymal stem cells (GMSC-EVs) as a therapeutic strategy for RA.

Roles of IRF4 in various immune cells in systemic lupus erythematosus.

Interferon regulatory factor 4 (IRF4) is a member of IRF family of transcription factors which mainly regulates the transcription of IFN. IRF4 is restrictively expressed in immune cells such as T and B cells, macrophages, as well as DC. It is essential for the development and function of these cells.

Heterogeneous ferroptosis susceptibility of macrophages caused by focal iron overload exacerbates rheumatoid arthritis.

Focal iron overload is frequently observed in patients with rheumatoid arthritis (RA), yet its functional significance remains elusive. Herein, we report that iron deposition in lesion aggravates arthritis by inducing macrophage ferroptosis. We show that excessive iron in synovial fluid positively correlates with RA disease severity as does lipid hyperoxidation of focal monocyte/macrophages.

Epithelial SIRT6 governs IL-17A pathogenicity and drives allergic airway inflammation and remodeling.

Dysregulation of IL-17A is closely associated with airway inflammation and remodeling in severe asthma. However, the molecular mechanisms by which IL-17A is regulated remain unclear. Here we identify epithelial sirtuin 6 (SIRT6) as an epigenetic regulator that governs IL-17A pathogenicity in severe asthma.

Targeting kinase ITK treats autoimmune arthritis via orchestrating T cell differentiation and function.

IL-2 inducible T cell kinase (ITK) is critical in T helper subset differentiation and its inhibition has been suggested for the treatment of T cell-mediated inflammatory diseases. T follicular helper (Tfh), Th17 and regulatory T cells (Treg) also play important roles in the development of rheumatoid arthritis (RA), while the role of ITK in the development of RA and the intricate balance between effector T and regulatory T cells remains unclear. Here, we found that CD4 T cells from RA patients presented with an elevated ITK activation.

Infusion of GMSCs relieves autoimmune arthritis by suppressing the externalization of neutrophil extracellular traps via PGE2-PKA-ERK axis.

Introduction: Rheumatoid arthritis (RA) is a systemic autoimmune disease with limited treatment success, characterized by chronic inflammation and progressive cartilage and bone destruction. Accumulating evidence has shown that neutrophil extracellular traps (NETs) released by activated neutrophils are important for initiating and perpetuating synovial inflammation and thereby could be a promising therapeutic target for RA. K/B × N serum transfer-induced arthritis (STIA) is a rapidly developed joint inflammatory model that somehow mimics the inflammatory response in patients with RA.

NFIL3 deficiency alleviates EAE through regulating different immune cell subsets.

Introduction: The transcription factor NFIL3 exerts comprehensive effects on the immune system. Previous studies revealed that NFIL3 is related to the function and development of different immune cell subsets. Experimental autoimmune encephalomyelitis (EAE) is mediated by immune cells which results in inflammatory demyelination in the central nervous system (CNS).

Neuropilin-1 Identifies a New Subpopulation of TGF-β-Induced Foxp3 Regulatory T Cells With Potent Suppressive Function and Enhanced Stability During Inflammation.

CD4Foxp3 regulatory T cells (Tregs) play a crucial role in preventing autoimmunity and inflammation. There are naturally-derived in the thymus (tTreg), generated extrathymically in the periphery (pTreg), and induced culture (iTreg) with different characteristics of suppressiveness, stability, and plasticity. There is an abundance of published data on neuropilin-1 (Nrp-1) as a tTreg marker, but little data exist on iTreg.

TNF-α stimulation enhances the neuroprotective effects of gingival MSCs derived exosomes in retinal ischemia-reperfusion injury via the MEG3/miR-21a-5p axis.

Retinal ischemia-reperfusion injury (IRI) is one of the main pathogenic mechanisms of glaucoma, which are largely unknown, including neuroinflammation and neuronal death in the pathological process. In our previous studies, mesenchymal stem cells (MSCs) have been reported to play anti-inflammatory and neuroprotective roles. Additionally, conditioned culture medium (CM) of MSCs stimulated by TNF-α have achieved better antiallergic effects in an experimental allergic conjunctivitis mouse model.

CD177 modulates the function and homeostasis of tumor-infiltrating regulatory T cells.

Regulatory T (Treg) cells are one of the major immunosuppressive cell types in cancer and a potential target for immunotherapy, but targeting tumor-infiltrating (TI) Treg cells has been challenging. Here, using single-cell RNA sequencing of immune cells from renal clear cell carcinoma (ccRCC) patients, we identify two distinct transcriptional fates for TI Treg cells, Fate-1 and Fate-2. The Fate-1 signature is associated with a poorer prognosis in ccRCC and several other solid cancers.

TGF-β-induced CD4+ FoxP3+ regulatory T cell-derived extracellular vesicles modulate Notch1 signaling through miR-449a and prevent collagen-induced arthritis in a murine model.

CD4FOXP3 Treg cells are central to the maintenance of self-tolerance and can be defective in autoimmunity. In autoimmune rheumatic diseases, dysfunctional self-tolerance, is to a large extent, caused by insufficient Treg-cell activity. Although nTregs have therapeutic effects in vivo, their relative scarcity and slow rate of in vitro expansion hinder the application of nTreg therapy.

Microstructure and mechanical behaviors of tibia for collagen-induced arthritic mice treated with gingiva-derived mesenchymal stem cells.

Rheumatoid arthritis (RA) is a systemic polyarticular arthritis that primarily affects the small joints but also causes bone erosion in large joints. None of the currently existing treatment approaches is curable. In this study, the effects of human gingiva-derived mesenchymal stem cells (GMSCs) on collagen-induced arthritis (CIA) mice are examined by experimentally assessing the microstructure and mechanical behaviors of tibia.

Insulin signaling establishes a developmental trajectory of adipose regulatory T cells.

Systematic characterizations of adipose regulatory T (T) cell subsets and their phenotypes remain uncommon. Using single-cell ATAC-sequencing and paired single-cell RNA and T cell receptor (TCR) sequencing to map mouse adipose T cells, we identified CD73ST2 and CD73ST2 subsets with distinct clonal expansion patterns. Analysis of TCR-sharing data implied a state transition between CD73ST2 and CD73ST2 subsets.

Mesenchymal Stem Cell-Derived Exosomes: A Promising Biological Tool in Nanomedicine.

As nano-scale biological vesicles, extracellular vesicles (EVs)/exosomes, in particular, exosomes derived from mesenchymal stem cells (MSC-exosomes), have been studied in the diagnosis, prevention, and treatment of many diseases. In addition, through the combination of nanotechnology and biotechnology, exosomes have emerged as innovative tools for the development of nanomedicine. This review focuses on a profound summarization of MSC-exosomes as a powerful tool in bionanomedicine.

Immunomodulatory Function of Vitamin D and Its Role in Autoimmune Thyroid Disease.

Vitamin D is one of the most important nutrients required by the human body. It is a steroid hormone that plays an important role in regulating calcium and phosphorus metabolism, and bone health. Epidemiological studies have revealed a close correlation between vitamin D and many common chronic diseases.

Proteolysis-targeting chimera against BCL-X destroys tumor-infiltrating regulatory T cells.

Regulatory T cells (Tregs) play an important role in maintaining immune homeostasis and, within tumors, their upregulation is common and promotes an immunosuppressive microenvironment. Therapeutic strategies that can eliminate Tregs in the tumor (i.e.

Regulatory T Cells: Concept, Classification, Phenotype, and Biological Characteristics.

Regulatory T cells (Treg) play an indispensable role in maintaining the body's immune nonresponse to self-antigens and suppressing the body's unwarranted and potentially harmful immune responses. Their absence, reduction, dysfunction, transformation, and instability can lead to numerous autoimmune diseases. There are several distinct subtypes of the Treg cells, although they share certain biological characteristics and have unique phenotypes with different regulatory functions, as well as mechanistic abilities.