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galectin 9 autoimmune

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https://www.readbyqxmd.com/read/28877989/regulatory-t-cell-mediated-suppression-of-inflammation-induced-by-dr3-signaling-is-dependent-on-galectin-9
#1
Shravan Madireddi, So-Young Eun, Amit K Mehta, Aruna Birta, Dirk M Zajonc, Toshiro Niki, Mitsuomi Hirashima, Eckhard R Podack, Taylor H Schreiber, Michael Croft
Stimulation of several TNF receptor family proteins has been shown to dampen inflammatory disease in murine models through augmenting the number and/or activity of regulatory T cells (Tregs). We recently found that one molecule, 4-1BB, used binding to Galectin-9 to exert its immunosuppressive effects and drive expansion of CD8(+)Foxp3(-) Tregs. We now show that ligation of another TNFR family molecule, DR3, which has previously been found to strongly expand CD4(+)Foxp3(+) Tregs and suppress inflammation, also requires Galectin-9...
September 6, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28830298/left-atrial-volume-index-in-patients-with-heart-failure-and-severely-impaired-left-ventricular-systolic-function-the-role-of-established-echocardiographic-parameters-circulating-cystatin-c-and-galectin-3
#2
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)...
August 1, 2017: Therapeutic Advances in Cardiovascular Disease
https://www.readbyqxmd.com/read/28810662/galectin-9-binds-to-o-glycans-on-protein-disulfide-isomerase
#3
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
https://www.readbyqxmd.com/read/28756232/tim3-galectin-9-alleviates-the-inflammation-of-tao-patients-via-suppressing-akt-nf-kb-signaling-pathway
#4
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
https://www.readbyqxmd.com/read/28534962/galectin%C3%A2-9-ameliorates-fulminant-liver-injury
#5
Tomoko Tadokoro, Asahiro Morishita, Teppei Sakamoto, Shintaro Fujihara, Koji Fujita, Shima Mimura, Kyoko Oura, Takako Nomura, Joji Tani, Hirohito Yoneyama, Hisakazu Iwama, Takashi Himoto, Toshiro Niki, Mitsuomi Hirashima, Tsutomu Masaki
Fulminant hepatitis is a severe liver disease resulting in hepatocyte necrosis. Galectin‑9 (Gal‑9) is a tandem‑repeat‑type galectin that has been evaluated as a potential therapeutic agent for various diseases that regulate the host immune system. Concanavalin A (ConA) injection into mice results in serious, immune‑mediated liver injury similar to human viral, autoimmune and fulminant hepatitis. The present study investigated the effects of Gal‑9 treatment on fulminant hepatitis in vivo and the effect on the expression of microRNAs (miRNAs), in order to identify specific miRNAs associated with the immune effects of Gal‑9...
July 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28152393/molecular-cloning-characterization-and-expression-analysis-of-tim-3-and-galectin-9-in-the-woodchuck-model
#6
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
https://www.readbyqxmd.com/read/27792886/tim-3-expression-on-immune-cells-and-roles-at-the-maternal-fetal-interface
#7
REVIEW
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
https://www.readbyqxmd.com/read/27394439/expression-of-human-t-cell-immunoglobulin-domain-and-mucin-3-tim-3-and-tim-3-ligands-in-peripheral-blood-from-patients-with-systemic-lupus-erythematosus
#8
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
https://www.readbyqxmd.com/read/26663989/serum-galectin-9-levels-are-associated-with-coronary-artery-disease-in-chinese-individuals
#9
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
https://www.readbyqxmd.com/read/26076826/increased-tim-3-expression-on-peripheral-t-lymphocyte-subsets-and-association-with-higher-disease-activity-in-systemic-lupus-erythematosus
#10
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
https://www.readbyqxmd.com/read/25880730/graves-disease-is-associated-with-a-defective-expression-of-the-immune-regulatory-molecule-galectin-9-in-antigen-presenting-dendritic-cells
#11
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
https://www.readbyqxmd.com/read/25760439/the-bitter-side-of-sweet-the-role-of-galectin-9-in-immunopathogenesis-of-viral-infections
#12
REVIEW
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
https://www.readbyqxmd.com/read/25304688/a-review-of-therapeutic-effects-of-mesenchymal-stem-cell-secretions-and-induction-of-secretory-modification-by-different-culture-methods
#13
REVIEW
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
https://www.readbyqxmd.com/read/25151395/galectins-and-neuroinflammation
#14
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
https://www.readbyqxmd.com/read/24958847/galectin-9-controls-the-therapeutic-activity-of-4-1bb-targeting-antibodies
#15
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
https://www.readbyqxmd.com/read/24756983/correlation-of-cxcl10-tumor-necrosis-factor-receptor-type-ii-and-galectin-9-with-disease-activity-in-juvenile-dermatomyositis
#16
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
https://www.readbyqxmd.com/read/24477688/galectin-9-ameliorates-anti-gbm-glomerulonephritis-by-inhibiting-th1-and-th17-immune-responses-in-mice
#17
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
https://www.readbyqxmd.com/read/24462947/direct-cytocidal-effect-of-galectin-9-localized-on-collagen-matrices-on-human-immune-cell-lines
#18
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
https://www.readbyqxmd.com/read/24383985/the-role-of-t-cell-immunoglobulin-and-mucin-domain-3-in-immune-thrombocytopenia
#19
REVIEW
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
https://www.readbyqxmd.com/read/24333756/the-tim-3-galectin-9-pathway-involves-in-the-homeostasis-of-hepatic-tregs-in-a-mouse-model-of-concanavalin-a-induced-hepatitis
#20
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
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