galectin 9 autoimmune

BACKGROUND: PD-1/PD-L1 engagement and overexpression of galectin-3 (Gal-3) are critical mechanisms of tumor-induced immune suppression that contribute to immunotherapy resistance. We hypothesized that Gal-3 blockade with belapectin (GR-MD-02) plus anti-PD-1 (pembrolizumab) would enhance tumor response in patients with metastatic melanoma (MM) and head and neck squamous cell carcinoma (HNSCC). METHODS: We performed a phase I dose escalation study of belapectin+pembrolizumab in patients with advanced MM or HNSCC (NCT02575404)...

Massive recruitment of eosinophils into the dermis is a hallmark of bullous pemphigoid pathogenesis. Identifying the chemoattractant(s) guiding eosinophils into the skin in bullous pemphigoid is a prerequisite to thera-peutic targeting of eosinophil recruitment. Galectin -9 is a potent chemoattractant for eosinophils, but its potential role in bullous pemphigoid is unknown. The aim of this study was to determine the expression levels of galectin-9 in serum and skin of patients with bullous pemphigoid. Galectin-9 levels were significantly elevated in serum of patients with bullous pemphigoid compared with age- and sex-matched controls, but did not correlate with disease activity assessed with the Bullous Pemphigoid Disease Area Index...

Pathologic roles of innate immunity in neurologic disorders are well described, but their beneficial aspects are less understood. Dectin-1, a C-type lectin receptor (CLR), is largely known to induce inflammation. Here, we report that Dectin-1 limited experimental autoimmune encephalomyelitis (EAE), while its downstream signaling molecule, Card9, promoted the disease. Myeloid cells mediated the pro-resolution function of Dectin-1 in EAE with enhanced gene expression of the neuroprotective molecule, Oncostatin M (Osm), through a Card9-independent pathway, mediated by the transcription factor NFAT...

BACKGROUND: Excretory-secretory (ES) products are crucial in maintaining helminths in the host. Consequently, the proteins of ES are potential vaccine molecules and potential therapeutic agents for autoimmune diseases. Heligmosomoides polygyrus bakeri, a gastrointestinal parasite of mice, is a model of hookworm infection in humans. ES produced by both sexes of H. polygyrus bakeri L4 stage cultured separately shows different immunomodulatory properties than ES obtained when both sexes are cultured together...

Galectin-9 (Gal-9) is a β-galactoside binding lectin known for its immunomodulatory role in various microbial infections. Gal-9 is expressed in all organ systems and localized in the nucleus, cell surface, cytoplasm and the extracellular matrix. It mediates host-pathogen interactions and regulates cell signalling via binding to its receptors. Gal-9 is involved in many physiological functions such as cell growth, differentiation, adhesion, communication and death. However, recent studies have emphasized on the elevated levels of Gal-9 in autoimmune disorders, viral infections, parasitic invasion, cancer, acute liver failure, atopic dermatitis, chronic kidney disease, type-2 diabetes, coronary artery disease, atherosclerosis and benign infertility-related gynecological disorders...

Type 1 diabetes occurs as a consequence of progressive autoimmune destruction of beta cells. A potential treatment for this disease should address the immune attack on beta cells and their preservation/regeneration. The objective of this study was to elucidate whether the immunomodulatory synthetic oligonucleotide IMT504 was able to ameliorate diabetes in NOD mice and to provide further understanding of its mechanism of action. We found that IMT504 restores glucose homeostasis in a diabetes mouse model similar to human type 1 diabetes, by regulating expression of immune modulatory factors and improving beta cell function...

Interstitial pneumonia with autoimmune features (IPAF) is an unexplained disease state characterized by autoimmunity and pulmonary fibrosis. Exploring the pathogenesis of IPAF is helpful for the treatment of interstitial pneumonia and idiopathic pulmonary fibrosis. In this study, we observed that the lung Galectin-9 (Gal-9) of IPAF patients was significantly reduced, which was significantly related to lung dysfunction and abnormal humoral immunity. Moreover, an overreactive germinal center (GC) reaction in the lung lymph nodes (LNs) of Gal-9-deficient mice was found to be related to abnormally active follicular helper T cells (Tfh) cells...

Humoral immunity is reliant on efficient recruitment of circulating naïve B cells from blood into peripheral lymph nodes (LN) and timely transition of naive B cells to high affinity antibody (Ab)-producing cells. Current understanding of factor(s) coordinating B cell adhesion, activation and differentiation within LN, however, is incomplete. Prior studies on naïve B cells reveal remarkably strong binding to putative immunoregulator, galectin (Gal)-9, that attenuates BCR activation and signaling, implicating Gal-9 as a negative regulator in B cell biology...

It is no longer controversial that atherosclerosis is a vascular wall chronic inflammatory disease mediated by cells of innate and adaptive immunity. Galectin-9 (Gal-9) seems to be a crucial regulator of T-cell immunity by inducing apoptosis in specific T-cell subpopulations associated with autoimmunity and inflammatory disease. Accumulating evidence showed that galectin-9 signaling via T-cell immunoglobulin mucin 3 (TIM-3) is concerned with different regulatory functions in autoimmunity, including direct depletion of pro-inflammatory T-cells, expanding the number of regulatory T cells, altering macrophages to an anti-inflammatory state and the induction of repressive myeloid-derived suppressor cells...

OBJECTIVE: T cell immunoglobulin and mucin-domain-containing molecule 3 (TIM-3) is implicated in the development of various autoimmune diseases. We aimed to investigate the levels of soluble TIM-3 (sTIM-3) and their associations between clinical parameters in patients with systemic lupus erythematosus (SLE). METHODS: Serum samples were collected from 65 patients with SLE and 35 age-matched healthy controls (HCs). The SLE Disease Activity Index 2000 (SLEDAI-2K) and the Systemic Lupus International Collaborating Clinics (SLICC) damage index (SDI) were used to assess SLE disease activity and SLE-related organ damage...

In various autoimmune diseases, Galecin-9 (Gal-9) has been shown to regulate the T-cell balance by decreasing Th1 and Th17, while increasing the number of regulatory T cells (Tregs). However, the role of Gal-9 in the patients with acute coronary syndrome (ACS) and chronic kidney disease (CKD) remains unclear. This study aims to measure the Gal-9 levels in serum and peripheral blood mononuclear cells (PBMCs) in patients with ACS plus CKD and examine their clinical implication. The serum levels of Gal-9 were determined by enzyme-linked immunosorbent assay (ELISA), the expression levels of Gal-9, Tim-3, and Foxp3 mRNA in PBMCs were detected by real-time reverse transcription-polymerase chain reaction (RT-PCR), and the expression of Gal-9 on the surface of PBMCs and in PBMCs was analyzed by flow cytometry...

OBJECTIVES: Vasculopathy is an important hallmark of systemic chronic inflammatory connective tissue diseases (CICTD) and is associated with increased cardiovascular risk. We investigated disease-specific biomarker profiles associated with endothelial dysfunction, angiogenic homeostasis and (tissue) inflammation, and their relation to disease activity in rare CICTD. METHODS: A total of 38 serum proteins associated with endothelial (dys)function and inflammation were measured by multiplex-immunoassay in treatment-naive patients with localized scleroderma (LoS, 30), eosinophilic fasciitis (EF, 8) or (juvenile) dermatomyositis (34), 119 (follow-up) samples during treatment, and 65 controls...

BACKGROUND: The interaction between galectin-9 (Gal-9) and its ligand, T cell immunoglobulin, and mucin-containing-molecule-3 (TIM-3), one of the coinhibitory receptors, transduce the inhibitory signaling to regulate immune responses. The dysregulated expression of checkpoint molecules has been reported under various inflammatory or autoimmune conditions. The aim of this study is to investigate the levels of these checkpoint molecules and their associations between proinflammatory markers in patients with adult Still's disease (ASD)...

: Galectin-1 (Gal-1) and galectin-3 (Gal-3) are carbohydrate-binding proteins involved in normal processes, autoimmunity, and cancer. Increased serum Gal-3 levels in scleroderma were associated with active disease, vasculopathy, and mortality. OBJECTIVES: The aim of this study was to evaluate Gal-1 and Gal-3 expression in the lesional skin of patients with scleroderma regarding disease severity and organ involvement. METHODS: A cross-sectional study was conducted on patients diagnosed as systemic sclerosis (SSc), after informed consent...

Hepatocytes are the targets in autoimmune hepatitis (AIH) that results in T cell-dependent liver injury. However, hepatocytes may also affect the hepatic T cells in AIH, but the underlying mechanisms are not fully understood. Here we report that hepatocytes could secrete galectin-9 (Gal-9) to suppress the intrahepatic production of Th1 cytokine IFN-γ and restrict AIH development, but hepatocyte damage resulted in opposite effects due to release of TLR2/4 ligands that promoted the intrahepatic production of IL-1β, IL-6, and IL-12...

The T cell immunoglobulin mucin molecule 3 (TIM-3), as a negative regulatory immune checkpoint, plays an important role in cellular immunity by binding to its ligand galectin-9 (Gal-9). Under abnormal conditions, this pathway can regulate the depletion of T cells and suppress the immune response. Abnormal expression of TIM-3 and Gal-9 has been confirmed in a variety of cancers, recurrent miscarriages, chronic infectious diseases and autoimmune diseases. More and more studies have shown that immune factors play an important role in the pathogenesis of adenomyosis...

BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by elevated interferon (IFN) signature genes. Galectin-9 (Gal-9) is a β-galactoside-binding lectin that is reportedly useful as a biomarker for IFN gene signatures. In a cross-sectional study of Japanese patients with recent-onset SLE, we aimed to determine whether raised serum Gal-9 levels were associated with the disease activity or organ damage seen in SLE patients. METHODS: The current study included 58 Japanese patients with SLE and 31 age-matched healthy individuals...

Galectin-9 is a risk gene in inflammatory bowel disease. By transcriptomic analyses of ileal biopsies and PBMCs from inflammatory bowel disease patients, we identified a positive correlation between galectin-9 expression and colitis severity. We observed that galectin-9-deficient T cells were less able to induce T cell-mediated colitis. However, several mouse-based studies reported that galectin-9 treatment induces T cell apoptosis and ameliorates autoimmune diseases in an exogenously modulated manner, indicating a complicated regulation of galectin-9 in T cells...

In recent years, research on glioma immunotherapy have grown rapidly. However, the autoimmune-like side effects that are caused by blocking immunological checkpoints hinder their clinical application in gliomas currently. Galectin-9, a ligand for T-cell immunoglobulin mucin 3, has shed a new light on the treatment of malignant glioma. However, the potential mechanism of Galectin-9 is still under discussion. In this study, first, we methodically gathered 1,027 glioma patients with RNA-seq and 986 patients with survival data to explore the role and mechanism of Galectin-9 in gliomas...

INTRODUCTION: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation and hyperplasia, as well as cartilage and bone destruction. Several proteins are associated with the pathogenesis of the disease. Galectin-9 belongs to the family of lectins that are involved in various biological processes and have anti-inflammatory activity. OBJECTIVE: To investigate associations between the SNPs of the GAL-9 gene (LGALS9) and serum levels in rheumatoid arthritis patients...