Galectin-8 Ameliorates Murine Autoimmune Ocular Pathology and Promotes a Regulatory T Cell Response.
James F. Sampson,Eiichi Hasegawa,Lama Mulki,Amol Suryawanshi,Shuhong Jiang,Wei-Sheng Chen,Gabriel A. Rabinovich,Kip M. Connor,Noorjahan Panjwani +8 more
TLDR
Treatment with Galectin-8 (Gal-8), a tandem-repeat member of the galectin family, reduces retinal pathology and prevents photoreceptor cell damage in a murine model of experimental autoimmune uveitis and emerges as an attractive therapeutic candidate not only for treating retinal autoimmune diseases, but also for other TH1- and TH17-mediated inflammatory disorders.Abstract:
Galectins have emerged as potent immunoregulatory agents that control chronic inflammation through distinct mechanisms. Here, we report that treatment with Galectin-8 (Gal-8), a tandem-repeat member of the galectin family, reduces retinal pathology and prevents photoreceptor cell damage in a murine model of experimental autoimmune uveitis. Gal-8 treatment increased the number of regulatory T cells (Treg) in both the draining lymph node (dLN) and the inflamed retina. Moreover, a greater percentage of Treg cells in the dLN and retina of Gal-8 treated animals expressed the inhibitory coreceptor cytotoxic T lymphocyte antigen (CTLA)-4, the immunosuppressive cytokine IL-10, and the tissue-homing integrin CD103. Treg cells in the retina of Gal-8-treated mice were primarily inducible Treg cells that lack the expression of neuropilin-1. In addition, Gal-8 treatment blunted production of inflammatory cytokines by retinal T helper type (TH) 1 and TH17 cells. The effect of Gal-8 on T cell differentiation and/or function was specific for tissues undergoing an active immune response, as Gal-8 treatment had no effect on T cell populations in the spleen. Given the need for rational therapies for managing human uveitis, Gal-8 emerges as an attractive therapeutic candidate not only for treating retinal autoimmune diseases, but also for other TH1- and TH17-mediated inflammatory disorders.read more
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Galectin-3 Is an Important Mediator of VEGF- and bFGF-Mediated Angiogenic Response
TL;DR: In this article, the authors demonstrate that galectin-3 is a mediator of vascular endothelial growth factor and basic fibroblast growth factor (bFGF)-mediated angiogenic response.
Journal ArticleDOI
The role of galectins in virus infection - A systemic literature review.
Wen Hung Wang,Chih Yen Lin,Max R. Chang,Aspiro Nayim Urbina,Wanchai Assavalapsakul,Arunee Thitithanyanont,Yen-Hsu Chen,Fu-Tong Liu,Sheng-Fan Wang +8 more
TL;DR: Information is offered regarding the various roles galectins shown in viral infection and it is suggested that galectin can potentially be used as viral therapeutic targets or antagonists.
Journal ArticleDOI
Re-wiring regulatory cell networks in immunity by galectin–glycan interactions
Ada G. Blidner,Santiago P. Méndez-Huergo,Alejandro J. Cagnoni,Gabriel A. Rabinovich,Gabriel A. Rabinovich +4 more
TL;DR: This work focuses on the emerging roles of galectins, a family of highly conserved glycan‐binding proteins in regulating the fate and function of regulatory immune cell populations, both of lymphoid and myeloid origins.
Journal ArticleDOI
Untangling Galectin-Driven Regulatory Circuits in Autoimmune Inflammation
Marta A. Toscano,Verónica Candela Martínez Allo,Anabela M. Cutine,Gabriel A. Rabinovich,Gabriel A. Rabinovich,Karina Mariño +5 more
TL;DR: Understanding the relevance of galectin-glycan interactions in autoimmune inflammation could help to uncover novel pathways of tolerance breakdown, define molecular signatures for patient stratification and therapy responses, and open new avenues for immune intervention.
Journal ArticleDOI
Suppression of age-related salivary gland autoimmunity by glycosylation-dependent galectin-1-driven immune inhibitory circuits.
Verónica Candela Martínez Allo,Vanesa Hauk,Nicolas Sarbia,Nicolás A. Pinto,Diego O. Croci,Tomás Dalotto-Moreno,Rosa M. Morales,Sabrina G. Gatto,Montana N Manselle Cocco,Juan C. Stupirski,Ángel Deladoey,Esteban Maronna,Priscila Marcaida,Virginia Durigan,Anastasia Secco,M. Mamani,Alicia Dos Santos,Antonio Catalan Pellet,Claudia Perez Leiros,Gabriel A. Rabinovich,Gabriel A. Rabinovich,Marta A. Toscano +21 more
TL;DR: It is demonstrated that aged Gal1-null mutant mice develop a spontaneous inflammatory process in salivary glands that resembles Sjögren’s syndrome, and endogenous Gal1 serves as a homeostatic rheostat that safeguards immune tolerance and prevents age-dependent development of spontaneous autoimmunity.
References
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Regulatory T Cells: Mechanisms of Differentiation and Function
TL;DR: Cellular and molecular mechanisms in the differentiation and function of regulatory T cells and their role in autoimmune and autoinflammatory disorders, allergy, acute and chronic infections, cancer, and metabolic inflammation are discussed.
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Oligosaccharide specificity of galectins: a search by frontal affinity chromatography.
Jun Hirabayashi,Tomomi Hashidate,Yoichiro Arata,Nozomu Nishi,Takanori Nakamura,Mitsuomi Hirashima,Tadasu Urashima,Toshihiko Oka,Masamitsu Futai,Werner E.G. Müller,Fumio Yagi,Ken-ichi Kasai +11 more
TL;DR: In this paper, a frontal affinity chromatography (FAC) was used to quantitatively analyze the interactions at 20 °C between 13 galectins including 16 CRDs originating from mammals, chick, nematode, sponge, and mushroom, with 41 pyridylaminated (PA) oligosaccharides.
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Turning 'sweet' on immunity: galectin-glycan interactions in immune tolerance and inflammation.
TL;DR: An improved understanding of the mechanisms underlying galectins' functions will provide further opportunities for developing new therapies based on the immunoregulatory properties of this multifaceted protein family.
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TH17 cells contribute to uveitis and scleritis and are expanded by IL-2 and inhibited by IL-27/STAT1
Ahjoku Amadi-Obi,Cheng-Rong Yu,Xuebin Liu,Rashid M. Mahdi,Grace Clarke,Robert B. Nussenblatt,Igal Gery,Yun Sang Lee,Charles E. Egwuagu +8 more
TL;DR: The findings suggest that TH1 cells may mitigate uveitis by antagonizing the TH17 phenotype through the IFN-γ–mediated induction of IL-27 in target tissue, and suggests that antagonism of TH17 by IFn-γ and/or IL- 27 could be used for the treatment of chronic inflammation.
Journal ArticleDOI
Either a Th17 or a Th1 effector response can drive autoimmunity: conditions of disease induction affect dominant effector category.
Dror Luger,Phyllis B. Silver,Jun Tang,Daniel J. Cua,Zoe Chen,Yoichiro Iwakura,Edward P. Bowman,Nicole Sgambellone,Chi-Chao Chan,Rachel R. Caspi +9 more
TL;DR: The data suggest that the dominant effector phenotype may be determined at least in part by conditions present during initial exposure to Ag, including the quality/quantity of Toll-like receptor stimulation and/or type of Ag-presenting cells.