Tolerogenic signals delivered by dendritic cells to T cells through a galectin-1-driven immunoregulatory circuit involving interleukin 27 and interleukin 10.
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.
Ilarregui
Juan M
JM
Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina.
Croci
Diego O
DO
Bianco
Germán A
GA
Toscano
Marta A
MA
Salatino
Mariana
M
Vermeulen
Mónica E
ME
Geffner
Jorge R
JR
Rabinovich
Gabriel A
GA
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*
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