title: Tolerogenic signals delivered by dendritic cells to T cells through a galectin-1-driven immunoregulatory circuit involving interleukin 27 and interleukin 10.
abstract: Despite their central function in orchestrating immunity, dendritic cells (DCs) can respond to inhibitory signals by becoming tolerogenic. Here we show that galectin-1, an endogenous glycan-binding protein, can endow DCs with tolerogenic potential. After exposure to galectin-1, DCs acquired an interleukin 27 (IL-27)-dependent regulatory function, promoted IL-10-mediated T cell tolerance and suppressed autoimmune neuroinflammation. Consistent with its regulatory function, galectin-1 had its highest expression on DCs exposed to tolerogenic stimuli and was most abundant from the peak through the resolution of autoimmune pathology. DCs lacking galectin-1 had greater immunogenic potential and an impaired ability to halt inflammatory disease. Our findings identify a tolerogenic circuit linking galectin-1 signaling, IL-27-producing DCs and IL-10-secreting T cells, which has broad therapeutic implications in immunopathology.
authors: Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina.
authors: Juan M
authors: JM
authors: Ilarregui
authors: Diego O
authors: DO
authors: Croci
authors: Germán A
authors: GA
authors: Bianco
authors: Marta A
authors: MA
authors: Toscano
authors: Mariana
authors: M
authors: Salatino
authors: Mónica E
authors: ME
authors: Vermeulen
authors: Jorge R
authors: JR
authors: Geffner
authors: Gabriel A
authors: GA
authors: Rabinovich
mesh_terms: D000818:Animals; D019013:CD40 Antigens / Q000502:physiology; D003713:Dendritic Cells / Q000502:physiology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology; D005260:Female; D037483:Galectin 1 / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000276:immunology; D007108:Immune Tolerance; D016753:Interleukin-10 / Q000502:physiology*; D007378:Interleukins / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments / Q000276:immunology; D050796:STAT3 Transcription Factor / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D019013:CD40 Antigens; D037483:Galectin 1; D006023:Glycoproteins; C486767:Il27 protein, mouse; D007378:Interleukins; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; C445081:myelin oligodendrocyte glycoprotein (35-55); D016753:Interleukin-10