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.

journal_name

Nat Immunol

journal_title

Nature immunology

authors

Ilarregui JM,Croci DO,Bianco GA,Toscano MA,Salatino M,Vermeulen ME,Geffner JR,Rabinovich GA

doi

10.1038/ni.1772

subject

Has Abstract

pub_date

2009-09-01 00:00:00

pages

981-91

issue

9

eissn

1529-2908

issn

1529-2916

pii

ni.1772

journal_volume

10

pub_type

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