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galectin 9 autoimmune

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...
October 20, 2016: Journal of Reproductive Immunology
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
Ruirui Zhu, Cheng Liu, Hongxia Tang, Qiutang Zeng, Xiang Wang, Zhengfeng Zhu, Yuzhou Liu, Xiaobo Mao, Yucheng Zhong
BACKGROUND: Recently, several studies suggest that galectin-9 (Gal-9) might play a pivotal role in the pathogenesis of autoimmune diseases. However, the exact role of Gal-9 in atherosclerosis remains to be elucidated. METHODS: Serum Gal-9, high-sensitivity C-reactive protein (hs-CRP), interferon- (IFN-) γ, interleukin- (IL-) 4, IL-17, and transforming growth factor- (TGF-) β1 were measured. The effect of Gal-9 on peripheral blood mononuclear cells (PBMC) was investigated in patients with normal coronary artery (NCA)...
2015: Mediators of Inflammation
Li-jun Song, Xiao Wang, Xu-ping Wang, Dong Li, Feng Ding, Hua-xiang Liu, Xiao Yu, Xing-fu Li, Qiang Shu
BACKGROUND: Both the T cell immunoglobulin domain- and mucin domain-containing molecule-3 (Tim-3) and the death receptor Fas contribute to the pathogenesis of various autoimmune diseases, including systemic lupus erythematosus (SLE). The aim of the present study was to determine whether Tim-3 and Fas are co-expressed on certain peripheral T lymphocyte subsets, and whether this expression is associated with greater disease activity in SLE. METHODS: Peripheral blood mononuclear cells were isolated from 46 patients newly diagnosed with SLE and 28 age- and sex-matched healthy controls (HCs)...
June 16, 2015: Diagnostic Pathology
Susanna Leskela, Ana Serrano, Hortensia de la Fuente, Ana Rodríguez-Muñoz, Ana Ramos-Levi, Miguel Sampedro-Nuñez, Francisco Sánchez-Madrid, Roberto González-Amaro, Mónica Marazuela
INTRODUCTION: Patients with autoimmune thyroid disease (AITD) show defects in their immune-regulatory mechanisms. Herein we assessed the expression and function of galectin-1 and galectin-9 (Gal-1, Gal-9) in dendritic cells (DCs) from patients with AITD. MATERIALS AND METHODS: Peripheral blood samples from 25 patients with Graves' disease (GD), 11 Hashimoto's thyroiditis (HT), and 24 healthy subjects were studied. Thyroid tissue samples from 44 patients with AITD and 22 patients with goiter were also analyzed...
2015: PloS One
Shahzma Merani, Wenna Chen, Shokrollah Elahi
In recent years, a critical role for β-galactoside-binding protein, Galectin-9 (Gal-9) has emerged in infectious disease, autoimmunity, and cancer. It is a ligand for T cell immunoglobulin mucin domain 3 (Tim-3), a type-I glycoprotein that is persistently expressed on dysfunctional T cells during chronic viral infections. Gal-9 exerts its pivotal immunomodulatory effects by inducing apoptosis or suppressing effector functions via engagement with its receptor, Tim-3. Recent studies report elevation of circulating Gal-9 in humans infected with different viral infections...
May 2015: Reviews in Medical Virology
Marialaura Madrigal, Kosagisharaf S Rao, Neil H Riordan
The mesenchymal stem cell (MSC) is being broadly studied in clinical trials. Contrary to the early paradigm of cell replacement and differentiation as a therapeutic mechanism of action, evidence is mounting that the secretions of the cells are responsible for their therapeutic effects. These secretions include molecules and extracellular vesicles that have both local and distant effects. This review summarizes the up- and down-regulation of MSC anti-inflammatory, immune modulating, anti-tumor, and regenerative secretions resulting from different stimuli including: a) hypoxia, which increases the production of growth factors and anti-inflammatory molecules; b) pro-inflammatory stimuli that induce the secretion of immune modulating and anti-inflammatory factors; and c) 3 dimensional growth which up regulates the production of anti-cancer factors and anti-inflammatory molecules compared to monolayer culture...
2014: Journal of Translational Medicine
Hung-Lin Chen, Fang Liao, Teng-Nan Lin, Fu-Tong Liu
Galectins, β-galactoside-binding lectins, play multiple roles in the regulation of immune and inflammatory responses. The major galectins expressed in the CNS are galectins 1, 3, 4, 8, and 9. Under normal physiological conditions, galectins maintain CNS homeostasis by participating in neuronal myelination, neuronal stem cell proliferation, and apical vesicle transport in neuronal cells. In neuronal diseases and different experimental neuroinflammatory disease models, galectins may serve as extracellular mediators or intracellular regulators in controlling the inflammatory response or conferring the remodeling capacity in damaged CNS tissues...
2014: Advances in Neurobiology
Shravan Madireddi, So-Young Eun, Seung-Woo Lee, Ivana Nemčovičová, Amit Kumar Mehta, Dirk M Zajonc, Nozomu Nishi, Toshiro Niki, Mitsuomi Hirashima, Michael Croft
Biologics to TNF family receptors are prime candidates for therapy of immune disease. Whereas recent studies have highlighted a requirement for Fcγ receptors in enabling the activity of CD40, TRAILR, and GITR when engaged by antibodies, other TNFR molecules may be controlled by additional mechanisms. Antibodies to 4-1BB (CD137) are currently in clinical trials and can both augment immunity in cancer and promote regulatory T cells that inhibit autoimmune disease. We found that the action of agonist anti-4-1BB in suppressing autoimmune and allergic inflammation was completely dependent on Galectin-9 (Gal-9)...
June 30, 2014: Journal of Experimental Medicine
F Bellutti Enders, F van Wijk, R Scholman, M Hofer, B J Prakken, A van Royen-Kerkhof, W de Jager
OBJECTIVE: Juvenile dermatomyositis (DM) is a systemic autoimmune disorder of unknown immunopathogenesis in which the immune system targets the microvasculature of skeletal muscles, skin, and other organs. The current mainstay of therapy is a steroid regimen in combination with other immunosuppressive treatments. To date, no validated markers for monitoring disease activity have been identified, which hampers personalized treatment. This study was undertaken to identify a panel of proteins specifically related to active disease in juvenile DM...
August 2014: Arthritis & Rheumatology
Qian Zhang, Hong Luan, Le Wang, Fan He, Huan Zhou, Xiaoli Xu, Xingai Li, Qing Xu, Toshiro Niki, Mitsuomi Hirashima, Gang Xu, Yongman Lv, Jin Yuan
Antiglomerular basement membrane glomerulonephritis (anti-GBM GN) is a Th1- and Th17-predominant autoimmune disease. Galectin-9 (Gal-9), identified as the ligand of Tim-3, functions in diverse biological processes and leads to the apoptosis of CD4(+)Tim-3(+) T cells. It is still unclear how Gal-9 regulates the functions of Th1 and Th17 cells and prevents renal injury in anti-GBM GN. In this study, Gal-9 was administered to anti-GBM GN mice for 7 days. We found that Gal-9 retarded the increase of Scr, ameliorated renal tubular injury, and reduced the formation of crescents...
April 15, 2014: American Journal of Physiology. Renal Physiology
Youko Fukata, Aiko Itoh, Yasuhiro Nonaka, Takashi Ogawa, Takanori Nakamura, Osamu Matsushita, Nozomu Nishi
BACKGROUND: There is a continuous demand for new immunosuppressive agents for organ transplantation. Galectin-9, a member of the galactoside-binding animal lectin family, has been shown to suppress pathogenic T-cell responses in autoimmune disease models and experimental allograft transplantation. In this study, an attempt has been made to develop new collagen matrices, which can cause local, contact-dependent immune suppression, using galectin-9 and collagen-binding galectin-9 fusion proteins as active ingredients...
June 2014: Biochimica et Biophysica Acta
X-M Zhang, N-N Shan
T cell immunoglobulin and mucin domain-3 (TIM-3), originally identified as a T helper (Th) 1-specific type I membrane protein, plays a vital role in Th1 immunity and tolerance induction through interaction with its ligand, galectin-9. The binding of TIM-3 by galectin-9 serves to downregulate Th1 responses. Moreover, the regulatory function of TIM-3 has been extended to other cells, such as Th17 cells, CD4(+) CD25(+) regulatory T cells (Tregs), CD8(+) T cells and certain innate immune cells. Previous studies have acknowledged that the TIM-3 pathway is involved in the pathogenesis of several human autoimmune diseases, such as systemic lupus erythematous, rheumatoid arthritis and aplastic anaemia...
April 2014: Scandinavian Journal of Immunology
Ying Ju, Xuming Shang, Zhanfeng Liu, Ji Zhang, Yuantang Li, Yajuan Shen, Yiqing Liu, Chunmei Liu, Bin Liu, Liyun Xu, Yong Wang, Bingchang Zhang, Jianwen Zou
T cell immunoglobulin- and mucin-domain-containing molecule-3 (Tim-3) is a negative regulator of interferon (IFN)-γ-secreting CD4(+) Th1 cells and plays a key role in autoimmune diseases. Here, we report that galectin-9 expression was increased in hepatic CD4(+)CD25(+) T cells in a mouse model of concanavalin A (Con A)-induced hepatitis. Moreover, Tim-3 showed increased levels in CD4(+)CD25(+) Foxp3(+) regulatory T cells (Tregs). Further analyses showed that blocking the Tim-3/galectin-9 pathway resulted in the suppression of Tregs in vitro, thereby significantly increasing interferon (IFN)-γ production from hepatic Teffs...
March 2014: Molecular Immunology
Takashi Kadowaki, Asahiro Morishita, Toshiro Niki, Junko Hara, Miwa Sato, Joji Tani, Hisaaki Miyoshi, Hirohito Yoneyama, Tsutomu Masaki, Toshio Hattori, Akihiro Matsukawa, Mitsuomi Hirashima
INTRODUCTION: Galectin-9 ameliorates various inflammatory conditions including autoimmune diseases by regulating T cell and macrophage/dendritic cell (DC) functions. However, the effect of galectin-9 on polymicrobial sepsis has not been assessed. METHODS: We induced polymicrobial sepsis by cecal ligation and puncture (CLP) in mice. The survival rate was compared between galectin-9- and PBS-treated CLP mice. An ELISA was used to compare the levels of various cytokines in the plasma and culture supernatants...
December 9, 2013: Critical Care: the Official Journal of the Critical Care Forum
Christopher Ungerer, Patricia Quade-Lyssy, Heinfried H Radeke, Reinhard Henschler, Christoph Königs, Ulrike Köhl, Erhard Seifried, Jörg Schüttrumpf
Therapeutic approaches using multipotent mesenchymal stromal cells (MSCs) are advancing in regenerative medicine, transplantation, and autoimmune diseases. The mechanisms behind MSC immune modulation are still poorly understood and the prediction of the immune modulatory potential of single MSC preparations remains a major challenge for possible clinical applications. Here, we highlight galectin-9 (Gal-9) as a novel, important immune modulator expressed by MSCs, which is strongly upregulated upon activation of the cells by interferon-γ (IFN-γ)...
April 1, 2014: Stem Cells and Development
Suleyman Serdar Koca, Fatma Akbas, Metin Ozgen, Servet Yolbas, Nevin Ilhan, Baris Gundogdu, Ahmet Isik
Systemic sclerosis (SSc) is an autoimmune disease of unknown etiology characterized by progressive fibrosis. Activated fibroblasts are mainly responsible for fibrosis in SSc. Galectin-3, a β-galactoside-binding lectin, plays many important regulatory roles in both physiological and pathological processes including proliferation, apoptosis, inflammation, and fibrosis. The purpose of this study was to assess the serum galectin-3 levels in patients with SSc. Thirty-seven SSc patients, 23 systemic lupus erythematosus (SLE) patients (serving as patient control group), and 28 healthy volunteers were enrolled in this study...
February 2014: Clinical Rheumatology
Friederike Gieseke, Anne Kruchen, Nikolay Tzaribachev, Frank Bentzien, Massimo Dominici, Ingo Müller
Human multipotent mesenchymal stromal cells (MSCs) are clinically applied to treat autoimmune diseases and graft-versus-host disease due to their immunomodulatory properties. Several molecules have been identified to mediate these effects, including constitutively expressed galectin-1. However, there are indications in the literature that MSCs exert enhanced immunosuppressive functions after interaction with an inflammatory environment. Therefore, we analyzed how inflammatory stimuli influence the expression of the galectin network in MSCs and functionally tested the relevance for the immunomodulatory effects of MSCs...
October 2013: European Journal of Immunology
Marloes J M Gooden, Valerie R Wiersma, Douwe F Samplonius, Jurjen Gerssen, Robert J van Ginkel, Hans W Nijman, Mitsuomi Hirashima, Toshiro Niki, Paul Eggleton, Wijnand Helfrich, Edwin Bremer
Galectin-9 (Gal-9) is known for induction of apoptosis in IFN-γ and IL-17 producing T-cells and amelioration of autoimmunity in murine models. On the other hand, Gal-9 induced IFN-γ positive T-cells in a sarcoma mouse model and in food allergy, suggesting that Gal-9 can have diametric effects on T-cell immunity. Here, we aimed to delineate the immunomodulatory effect of Gal-9 on human resting and ex vivo activated peripheral blood lymphocytes. Treatment of resting lymphocytes with low concentrations of Gal-9 (5-30 nM) induced apoptosis in ∼60% of T-cells after 1 day, but activated the surviving T-cells...
2013: PloS One
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