Mitochondrial reactive oxygen species regulate acetyl-CoA flux between cytokine production and fatty acid synthesis in effector T cells.

Genetic and environmental factors shape an individual's susceptibility to autoimmunity. To identify genetic variations regulating effector T cell functions, we used a forward genetics screen of inbred mouse strains and uncovered genomic loci linked to cytokine expression. Among the candidate genes, we characterized a mitochondrial inner membrane protein, TMEM11, as an important determinant of Th1 responses.

STING-STAT6 Signaling Pathway Promotes IL-4 and IFN-α Fibrotic T Cell Activation and Exacerbates Scleroderma in SKG Mice.

Systemic sclerosis (SS) is an autoimmune disease and pathological mechanisms of SS are unclear. In this study, we investigated the role of T cells in the progression of SS using SKG mice and humanized mice. SKG mice have a spontaneous point mutation in ZAP70.

Fingolimod, an antagonist of sphingosine 1-phosphate, ameliorates Sjögren's syndrome by reducing the number of STAT3-induced germinal center B cells and increasing the number of Breg cells.

Background: Sjögren's syndrome (SS) is an autoimmune disease caused by infiltrating lymphocytes. FTY720 affects the S1P signaling pathway, which plays a role in T and B cell migration from secondary lymphoid tissues to target organs. In this study, we investigate the regulatory mechanism of FTY720 in the context of SS.

IL-21 drives skin and lung inflammation and fibrosis in a model for systemic sclerosis.

Background: Systemic sclerosis (SSc) is an autoimmune disease characterized by vasculopathy, abnormal inflammation, and fibrosis of the skin and internal organs, notably the skin and lungs, significantly impairing quality of life. There is currently no cure for SSc, and its etiology remains largely unknown, presenting a primary barrier to effective treatment. We investigated the role of interleukin-21 (IL-21) in the pathogenesis of SSc.

Gut microbiome-derived butyrate inhibits the immunosuppressive factors PD-L1 and IL-10 in tumor-associated macrophages in gastric cancer.

Early detection and surgical treatment are essential to achieve a good outcome in gastric cancer (GC). Stage IV and recurrent GC have a poor prognosis. Therefore, new treatments for GC are needed.

SARS-CoV-2 spike protein accelerates systemic sclerosis by increasing inflammatory cytokines, Th17 cells, and fibrosis.

Background: Coronavirus disease 2019 (COVID-19) induces a dysfunctional immune response, inflammation, autoantibody production, and coagulopathy, which are symptoms that bear resemblance to those of autoimmune diseases, including systemic sclerosis (SSc).

Methods: While there is a single case report suggesting an association between COVID-19 and SSc, the effects of COVID-19 on SSc are not yet fully understood. Human embryonic kidney 293 (HEK293) cells were transfected with the SARS-CoV-2 spike protein gene, in the presence of TGF-β.

Effect of IL-10-producing B cells in peripheral blood and tumor tissue on gastric cancer.

Background: Interleukin (IL)-10-producing B (B10) cells are generated in response to signals from the tumor microenvironment and promote tumor growth by interacting with B10 cells. We investigated the distributions of immune cells in peripheral blood and tumor tissue samples from patients with gastric cancer (GC).

Methods: Patients with GC who underwent radical gastrectomy in Seoul St.

Tripartite Motif-Containing Protein 32 (TRIM32): What Does It Do for Skeletal Muscle?

Tripartite motif-containing protein 32 (TRIM32) is a member of the tripartite motif family and is highly conserved from flies to humans. Via its E3 ubiquitin ligase activity, TRIM32 mediates and regulates many physiological and pathophysiological processes, such as growth, differentiation, muscle regeneration, immunity, and carcinogenesis. TRIM32 plays multifunctional roles in the maintenance of skeletal muscle.

Lactobacillus acidophilus and propionate attenuate Sjögren's syndrome by modulating the STIM1-STING signaling pathway.

Background: Sjögren's syndrome (SS) is an autoimmune disease characterized by inflammation of the exocrine gland. An imbalance of gut microbiota has been linked to SS. However, the molecular mechanism is unclear.

SARS-CoV-2 spike protein promotes inflammatory cytokine activation and aggravates rheumatoid arthritis.

Background: Coronavirus disease 2019 (COVID-19) induces inflammation, autoantibody production, and thrombosis, which are common symptoms of autoimmune diseases, including rheumatoid arthritis (RA). However, the effect of COVID-19 on autoimmune disease is not yet fully understood.

Methods: This study was performed to investigate the effects of COVID-19 on the development and progression of RA using a collagen-induced arthritis (CIA) animal model.

Tripartite motif-containing protein 32 regulates Ca movement in skeletal muscle.

Mutations in tripartite motif-containing protein 32 (TRIM32), especially in NHL repeats, have been found in skeletal muscle in patients with type 2H limb-girdle muscular dystrophy (LGMD2H). However, the roles of the NHL repeats of TRIM32 in skeletal muscle functions have not been well addressed. In the present study, to examine the functional role(s) of the TRIM32 NHL repeats in skeletal muscle, TRIM32-binding proteins in skeletal muscle were first searched using a binding assay and MALDI-TOF/TOF.

(LA-1) and butyrate inhibit osteoarthritis by controlling autophagy and inflammatory cell death of chondrocytes.

Osteoarthritis (OA) reduces the quality of life as a result of the pain caused by continuous joint destruction. Inactivated (LA-1) ameliorated osteoarthritis and protected cartilage by modulating inflammation. In this study, we evaluated the mechanism by which live LA-1 ameliorated OA.

Soluble CCR2 gene therapy controls joint inflammation, cartilage damage, and the progression of osteoarthritis by targeting MCP-1 in a monosodium iodoacetate (MIA)-induced OA rat model.

Background: Osteoarthritis (OA) is the most common type of degenerative arthritis and affects the entire joint, causing pain, joint inflammation, and cartilage damage. Various risk factors are implicated in causing OA, and in recent years, a lot of research and interest have been directed toward chronic low-grade inflammation in OA. Monocyte chemoattractant protein-1 (MCP-1; also called CCL2) acts through C-C chemokine receptor type 2 (CCR2) in monocytes and is a chemotactic factor of monocytes that plays an important role in the initiation of inflammation.

Inner-Membrane-Bound Gold Nanoparticles as Efficient Electron Transfer Mediators for Enhanced Mitochondrial Electron Transport Chain Activity.

Electron transfer through the mitochondrial electron transport chain (ETC) can be critically blocked by the dysfunction of protein complexes. Redox-active molecules have been used to mediate the electron transfer in place of the dysfunctional complexes; however, they are limited to replacing complex I and are known to be toxic. Here we report artificial mitochondrial electron transfer pathways that enhance ETC activity by exploiting inner-membrane-bound gold nanoparticles (GNPs) as efficient electron transfer mediators.

Vitamin D Attenuates Pain and Cartilage Destruction in OA Animals via Enhancing Autophagic Flux and Attenuating Inflammatory Cell Death.

Osteoarthritis (OA) is the most common form of arthritis associated with ageing. Vitamin D has diverse biological effect on bone and cartilage, and observational studies have suggested it potential benefit in OA progression and inflammation process. However, the effect of vitamin D on OA is still contradictory.

Coenzyme Q10 encapsulated in micelles ameliorates osteoarthritis by inhibiting inflammatory cell death.

Background: Osteoarthritis (OA) is the most common degenerative joint disease and is characterized by breakdown of joint cartilage. Coenzyme Q10 (CoQ10) exerts diverse biological effects on bone and cartilage; observational studies have suggested that CoQ10 may slow OA progression and inflammation. However, any effect of CoQ10 on OA remains unclear.

Ca Signaling Augmented by ORAI1 Trafficking Regulates the Pathogenic State of Effector T Cells.

Activation of the Ca release-activated Ca (CRAC) channel is crucial for T cell functions. It was recently shown that naked cuticle homolog 2 (NKD2), a signaling adaptor molecule, orchestrates trafficking of ORAI1, a pore subunit of the CRAC channels, to the plasma membrane for sustained activation of the CRAC channels. However, the physiological role of sustained Ca entry via ORAI1 trafficking remains poorly understood.

FK506 and Lactobacillus acidophilus ameliorate acute graft-versus-host disease by modulating the T helper 17/regulatory T-cell balance.

Background: Graft-versus-host disease (GvHD) is a critical complication after allogeneic hematopoietic stem cell transplantation (HSCT). The immunosuppressants given to patients undergoing allogeneic HSCT disturb the microbiome and the host immune system, potentially leading to dysbiosis and inflammation, and may affect immune function and bone marrow transplantation. The intestinal microbiome is a target for the development of novel therapies for GvHD.

Calsequestrin 1 Is an Active Partner of Stromal Interaction Molecule 2 in Skeletal Muscle.

Calsequestrin 1 (CASQ1) in skeletal muscle buffers and senses Ca in the sarcoplasmic reticulum (SR). CASQ1 also regulates store-operated Ca entry (SOCE) by binding to stromal interaction molecule 1 (STIM1). Abnormal SOCE and/or abnormal expression or mutations in CASQ1, STIM1, or STIM2 are associated with human skeletal, cardiac, or smooth muscle diseases.

IL-17 and CCR9α4β7 Th17 Cells Promote Salivary Gland Inflammation, Dysfunction, and Cell Death in Sjögren's Syndrome.

Previous studies have evaluated the roles of T and B cells in the pathogenesis of Sjögren's syndrome (SS); however, their relationships with age-dependent and metabolic abnormalities remain unclear. We examined the impacts of changes associated with aging or metabolic abnormalities on populations of T and B cells and SS disease severity. We detected increased populations of IL-17-producing T and B cells, which regulate inflammation, in the salivary glands of NOD/ShiLtJ mice.

NKD2 mediates stimulation-dependent ORAI1 trafficking to augment Ca entry in T cells.

Sustained activation of the Ca-release-activated Ca (CRAC) channel is pivotal for effector T cell responses. The mechanisms underlying this sustainability remain poorly understood. We find that plasma membrane localization of ORAI1, the pore subunit of CRAC channels, is limited in effector T cells, with a significant fraction trapped in intracellular vesicles.