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galectin 3 autoimmune

Cristian Gabriel Beccaria, María Carolina Amezcua Vesely, Facundo Fiocca Vernengo, Ricardo Carlos Gehrau, María Cecilia Ramello, Jimena Tosello Boari, Melisa Gorosito Serrán, Juan Mucci, Eliane Piaggio, Oscar Campetella, Eva Virginia Acosta Rodríguez, Carolina Lucía Montes, Adriana Gruppi
Germinal centers (GC) are important sites for high-affinity and long-lived antibody induction. Tight regulation of GC responses is critical for maintaining self-tolerance. Here, we show that Galectin-3 (Gal-3) is involved in GC development. Compared with WT mice, Gal-3 KO mice have more GC B cells and T follicular helper cells, increased percentages of antibody-secreting cells and higher concentrations of immunoglobulins and IFN-γ in serum, and develop a lupus-like disease. IFN-γ blockade in Gal-3 KO mice reduces spontaneous GC formation, class-switch recombination, autoantibody production and renal pathology, demonstrating that IFN-γ overproduction sustains autoimmunity...
April 24, 2018: Nature Communications
Sonia Zeggar, Katsue S Watanabe, Sanae Teshigawara, Sumie Hiramatsu, Takayuki Katsuyama, Eri Katsuyama, Haruki Watanabe, Yoshinori Matsumoto, Tomoko Kawabata, Ken-Ei Sada, Toshiro Niki, Mitsuomi Hirashima, Jun Wada
OBJECTIVE: In systemic lupus erythematosus (SLE), an autoimmune disease associated with multiple organ involvements, lupus nephritis determines prognosis and arthritis impairs quality of life of patients. Galectin-9 (Gal-9, Lgals9) is a β-galactoside binding lectin and the attempts for its clinical application have been made in autoimmune diseases, since recombinant Gal-9 as a ligand for Tim-3 induces apoptosis in activated CD4+ Tim-3+ Th1 cell. We investigated wethere the deficiency of Lgals9 is beneficial or deleterious in lupus mice models...
February 26, 2018: Arthritis & Rheumatology
Ken Shirabe, Yuki Bekki, Dolgormaa Gantumur, Kenichiro Araki, Norihiro Ishii, Atsushi Kuno, Hisashi Narimatsu, Masashi Mizokami
Assessing liver fibrosis is important for predicting the efficacy of antiviral therapy and patient prognosis. Liver biopsy is the gold standard for diagnosing liver fibrosis, despite its invasiveness and problematic diagnostic accuracy. Although noninvasive techniques to assess liver fibrosis are becoming important, reliable serum surrogate markers are not available. A glycoproteomics study aimed at identifying such markers discovered Mac 2-Binding Protein Gylcan Isomer (M2BPGi), which is a reliable marker for assessing liver fibrosis in patients with viral hepatitis and other fibrotic liver diseases such as primary biliary cholangitis, biliary atresia, autoimmune hepatitis, and nonalcoholic fatty liver disease...
January 9, 2018: Journal of Gastroenterology
S F Issa, A F Christensen, H M Lindegaard, M L Hetland, K Hørslev-Petersen, K Stengaard-Pedersen, B J Ejbjerg, T Lottenburger, T Ellingsen, J K Pedersen, K Junker, A Svendsen, U Tarp, M Østergaard, P Junker
Galectin-3 has been suggested as a pro-inflammatory mediator in animal arthritis and rheumatoid arthritis (RA). We aimed to study the serum level of galectin-3 in patients with newly diagnosed RA and associations with disease profile, Magnetic resonance imaging (MRI) findings and seromarkers of synovial matrix inflammation. One hundred and sixty DMARD naïve patients newly diagnosed with RA were included (CIMESTRA study). Clinical, serological and imaging data were recorded before treatment and at 6 weeks, 3 and 12 months...
December 2017: Scandinavian Journal of Immunology
Christos Zivlas, Filippos Triposkiadis, Stelios Psarras, Gregory Giamouzis, Ioannis Skoularigis, Stavros Chryssanthopoulos, Alkistis Kapelouzou, Steve Ramcharitar, Edward Barnes, Evangelos Papasteriadis, Dennis Cokkinos
Backround: Left atrial (LA) enlargement plays an important role in the development of heart failure (HF) and is a robust prognostic factor. Fibrotic processes have also been advocated to evoke HF through finite signalling proteins. METHODS: We examined the association of two such proteins, cystatin C (CysC) and galectin-3 (Gal-3), and other clinical, echocardiographic and biochemical parameters with LA volume index (LAVi) in patients with HF with severely impaired left ventricular ejection fraction (LVEF)...
November 2017: Therapeutic Advances in Cardiovascular Disease
Katrin Schaefer, Nicholas E Webb, Mabel Pang, Jenny E Hernandez-Davies, Katharine P Lee, Pascual Gonzalez, Martin V Douglass, Benhur Lee, Linda G Baum
Changes in the T cell surface redox environment regulate critical cell functions, such as cell migration, viral entry and cytokine production. Cell surface protein disulfide isomerase (PDI) contributes to the regulation of T cell surface redox status. Cell surface PDI can be released into the extracellular milieu or can be internalized by T cells. We have found that galectin-9, a soluble lectin expressed by T cells, endothelial cells and dendritic cells, binds to and retains PDI on the cell surface. While endogenous galectin-9 is not required for basal cell surface PDI expression, exogenous galectin-9 mediated retention of cell surface PDI shifted the disulfide/thiol equilibrium on the T cell surface...
September 1, 2017: Glycobiology
Li-Hua Luo, Dong-Mei Li, Yan-Ling Wang, Kang Wang, Li-Xin Gao, Shuang Li, Ji-Gang Yang, Chun-Lin Li, Wei Feng, Hong Guo
Thyroid-associated ophthalmopathy (TAO) is an autoimmune disease. Studies showed that T helper 1 (Th1), Th2, and Th17 cells play important roles in the pathology of TAO. Tim-3 and its only known ligand Galectin-9 (Gal-9) is related to the suppression of Th1 and Th17 cytokine secretion. This study aims to investigate the role of Tim3/Gal-9 in the inflammatory response of TAO. In this study, the levels of Tim3, Gal-9, and cytokines of Th1 (TNF-α and IFN-γ), Th2 (IL-4), and Th17 (IL-17) cells were analyzed in the blood samples of TAO patients and healthy controls as well as in orbital fibroblasts...
September 30, 2017: Biochemical and Biophysical Research Communications
Christoffer T Nielsen, Ole Østergaard, Niclas S Rasmussen, Søren Jacobsen, Niels H H Heegaard
Subcellular microvesicles (MVs) have attracted increasing interest during the past decades. While initially considered as inert cellular debris, several important roles for MVs in physiological homeostasis, cancer, cardiovascular, and autoimmune diseases have been uncovered. Although still poorly understood, MVs are involved in trafficking of information from cell-to-cell, and are implicated in the regulation of immunity, thrombosis, and coagulation. Different subtypes of extracellular MVs exist. This review focuses on the cell membrane-derived shedded MVs (ranging in size from 200 to 1000 nm) typically termed microparticles (MPs)...
2017: Clinical Proteomics
Yanan Liu, Junzhong Wang, Lu Wang, Baoju Wang, Shangqing Yang, Qin Wang, Jinzhuo Luo, Xuemei Feng, Xuecheng Yang, Yinping Lu, Michael Roggendorf, Mengji Lu, Dongliang Yang, Jia Liu
In recent years, a critical role for T cell immunoglobulin mucin domain 3 (Tim-3) and its ligand Galectin-9 (Gal-9) has emerged in infectious disease, autoimmunity and cancer. Manipulating this immune checkpoint may have immunotherapeutic potential and could represent an alternative approach for improving immune responses to viral infections and cancer. The woodchuck (Marmot monax) infected by woodchuck hepatitis virus (WHV) represents an informative animal model to study HBV infection and HCC. In the current study, the cDNA sequences of woodchuck Tim-3 and Gal-9 were cloned, sequenced and characterized...
March 2017: Molecular Immunology
Xiao-Hui Hu, Mao-Xing Tang, Gil Mor, Ai-Hua Liao
Successful pregnancy relies on the accurate regulation of the maternal-fetal immune system. Without enough tolerance in the uterine microenvironment, the mother and the hemiallogeneic fetus could not peacefully coexist. T cell immunoglobulin and mucin domain (Tim)-3 is a molecule originally regarded as to be expressed on terminally differentiated IFN-γ expressing CD4+ T cells (Th1). The engagement of Tim-3 with its ligand, galectin-9 (Gal-9) could induce the exhaustion or apoptosis of effector T cells, and thus might regulate the tolerance...
November 2016: Journal of Reproductive Immunology
Francesca Saccon, Mariele Gatto, Anna Ghirardello, Luca Iaccarino, Leonardo Punzi, Andrea Doria
Galectins are evolutionary conserved β-galactoside binding proteins with a carbohydrate-recognition domain (CRD) of approximately 130 amino acids. In mammals, 15 members of the galectin family have been identified and classified into three subtypes according to CRD organization: prototype, tandem repeat-type and chimera-type galectins. Galectin-3 (gal-3) is the only chimera type galectin in vertebrates containing one CRD linked to an unusual long N-terminal domain which displays non-lectin dependent activities...
January 2017: Autoimmunity Reviews
Jijing Tian, Guoxiang Yang, Huan-Yuan Chen, Daniel K Hsu, Alexey Tomilov, Kristin A Olson, Ali Dehnad, Sarah R Fish, Gino Cortopassi, Bin Zhao, Fu-Tong Liu, M Eric Gershwin, Natalie J Török, Joy X Jiang
Macrophage activation is an important feature of primary biliary cholangitis (PBC) pathogenesis and other cholestatic liver diseases. Galectin-3 (Gal3), a pleiotropic lectin, is produced by monocytic cells and macrophages. However, its role in PBC has not been addressed. We hypothesized that Gal3 is a key to induce NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome in macrophages and in turn to propagate proinflammatory IL-17 signaling. In liver tissues from patients with PBC and dnTGF-βRII mice, a model of autoimmune cholangitis, the expression of Gal3, NLRP3, and the adaptor protein adaptor apoptosis-associated speck-like protein was induced, with the downstream activation of caspase-1 and IL-1β...
December 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Qingqing Jiao, Qihong Qian, Zuotao Zhao, Fumin Fang, Xiaohan Hu, Jingnan An, Jian Wu, Cuiping Liu
Systemic lupus erythematosus (SLE) is a prototypic systemic autoimmune disease. The T cell immunoglobulin and mucin domain (TIM) family is associated with autoimmune diseases, but its level of expression in the immune cells of patients with SLE is still uncertain. The aim of this study was to examine whether TIM-3 and Galectin-9 (Gal-9) contribute to the pathogenesis of SLE. In total, 30 patients with SLE and 30 healthy controls were recruited, and their levels of TIM-3 expression in peripheral blood mononuclear cells (PBMCs) were examined via flow cytometry...
October 2016: Archives of Dermatological Research
Haik Mkhikian, Christie-Lynn Mortales, Raymond W Zhou, Khachik Khachikyan, Gang Wu, Stuart M Haslam, Patil Kavarian, Anne Dell, Michael Demetriou
Essential biological systems employ self-correcting mechanisms to maintain cellular homeostasis. Mammalian cell function is dynamically regulated by the interaction of cell surface galectins with branched N-glycans. Here we report that N-glycan branching deficiency triggers the Golgi to generate bioequivalent N-glycans that preserve galectin-glycoprotein interactions and cellular homeostasis. Galectins bind N-acetyllactosamine (LacNAc) units within N-glycans initiated from UDP-GlcNAc by the medial-Golgi branching enzymes as well as the trans-Golgi poly-LacNAc extension enzyme β1,3-N-acetylglucosaminyltransferase (B3GNT)...
June 8, 2016: ELife
Masaru Takeshita, Atsushi Kuno, Katsuya Suzuki, Atsushi Matsuda, Hiroko Shimazaki, Tomomi Nakagawa, Yuki Otomo, Yasuaki Kabe, Makoto Suematsu, Hisashi Narimatsu, Tsutomu Takeuchi
BACKGROUND: Nearly all secreted proteins are glycosylated, and serum glycoproteins that exhibit disease-associated glycosylation changes have potential to be biomarkers. In rheumatoid arthritis (RA), C-reactive protein (CRP), and matrix metalloproteinase-3 (MMP-3) are widely used as serologic biomarkers, but they lack sufficient specificity or precision. We performed comparative glycosylation profiling of MMP-3 using a recently developed antibody-overlay lectin microarray technology that allows semicomprehensive and quantitative analysis of specific protein glycosylation to develop an RA-specific disease activity biomarker...
May 21, 2016: Arthritis Research & Therapy
Aleksandar Arsenijevic, Marija Milovanovic, Jelena Milovanovic, Bojana Stojanovic, Natasa Zdravkovic, Patrick S C Leung, Fu-Tong Liu, M Eric Gershwin, Miodrag L Lukic
Galectin-3 (Gal-3) is a carbohydrate binding lectin, with multiple roles in inflammatory diseases and autoimmunity including its antiapoptotic effect on epithelial cells. In particular, increased expression of Gal-3 in epithelial cells is protective from apoptosis. Based on the thesis that apoptosis of biliary epithelial cells (BECs) is critical to the pathogenesis of Primary Biliary Cholangitis (PBC), we have analyzed the role of Gal-3 in the murine model of autoimmune cholangitis. We took advantage of Gal-3 knockout mice and immunized them with a mimotope of the major mitochondrial autoantigen of PBC, 2-octynoic acid (2-OA) coupled to BSA (2OA-BSA) and evaluated the natural history of subsequent disease, compared to control wild-type mice, by measuring levels of antibodies to PDC-E2, immunohistology of liver, and expression of Gal-3...
March 21, 2016: Scientific Reports
Christoffer T Nielsen, Niclas S Rasmussen, Niels H H Heegaard, Søren Jacobsen
Immune complex (IC) deposition in the glomerular basement membrane (GBM) is a key early pathogenic event in lupus nephritis (LN). The clarification of the mechanisms behind IC deposition will enable targeted therapy in the future. Circulating cell-derived microparticles (MPs) have been proposed as major sources of extracellular autoantigens and ICs and triggers of autoimmunity in LN. The overabundance of galectin-3-binding protein (G3BP) along with immunoglobulins and a few other proteins specifically distinguish circulating MPs in patients with systemic lupus erythematosus (SLE), and this is most pronounced in patients with active LN...
July 2016: Autoimmunity Reviews
Bojana Simovic Markovic, Aleksandar Nikolic, Marina Gazdic, Sanja Bojic, Ljubica Vucicevic, Milica Kosic, Slobodanka Mitrovic, Milos Milosavljevic, Gurdyal Besra, Vladimir Trajkovic, Nebojsa Arsenijevic, Miodrag L Lukic, Vladislav Volarevic
BACKGROUND AND AIMS: Galectin-3 [Gal-3] is an endogenous lectin with a broad spectrum of immunoregulatory effects: it plays an important role in autoimmune/inflammatory and malignant diseases, but the precise role of Gal-3 in pathogenesis of ulcerative colitis is still unknown. METHODS: We used a model of dextran sulphate sodium [DSS]-induced acute colitis. The role of Gal-3 in pathogenesis of this disease was tested by evaluating disease development in Gal-3 deficient mice and administration of Gal-3 inhibitor...
May 2016: Journal of Crohn's & Colitis
P A Mortarino, D P Goy, D B Abramson, J Cabello, G E Bumaguin, E J Vitelli, J Toledo, L Sarrio, S M Pezzotto, J P Mardegan Issa, G R Cointry, S Feldman
The induction of tolerance has been proposed as a therapeutic strategy for arthritis aiming to decrease progression of the pathology, probably by promoting suppressor mechanisms of the autoimmune response. This work aimed to confirm whether the treatment with vitamin D3 could synergize oral tolerance induced by hydrolyzed collagen peptides, in our experimental model of antigen induced arthritis in New Zealand rabbits. Clinical observation of the phenomenon indicates that simultaneous treatment with hydrolyzed collagen peptides and vitamin D3 was beneficial when compared with no treatment, for arthritic animals, and for arthritic animals that received treatment with only hydrolyzed collagen peptides or vitamin D3...
February 2016: Microscopy Research and Technique
Priya Chaudhary, Gail Marracci, Danielle Galipeau, Edvinas Pocius, Brooke Morris, Dennis Bourdette
Cortical lesions are a crucial part of MS pathology and it is critical to determine that new MS therapies have the ability to alter cortical inflammatory lesions given the differences between white and gray matter lesions. We tested lipoic acid (LA) in a mouse focal cortical EAE model. Brain sections were stained with antibodies against CD4, CD11b and galectin-3. Compared with vehicle, treatment with LA significantly decreased CD4+ and galectin-3+ immune cells in the brain. LA treated mice had fewer galectin-3+ cells with no projections indicating decrease in the number of infiltrating monocytes...
December 15, 2015: Journal of Neuroimmunology
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