Unknown

Dataset Information

0

Ly9 (CD229) Cell-Surface Receptor is Crucial for the Development of Spontaneous Autoantibody Production to Nuclear Antigens.


ABSTRACT: The Signaling Lymphocyte Activation Molecule Family (SLAMF) genes, which encode cell-surface receptors that modulate innate and adaptive immune responses, lay within a genomic region of human and mouse chromosome 1 that confers a predisposition for the development of systemic lupus erythematosus (SLE). Herein, we demonstrate that the SLAMF member Ly9 arises as a novel receptor contributing to the reinforcement of tolerance. Specifically, Ly9-deficient mice spontaneously developed features of systemic autoimmunity such as the production of anti-nuclear antibodies (ANA), -dsDNA, and -nucleosome autoantibodies, independently of genetic background [(B6.129) or (BALB/c.129)]. In aged (10- to 12-month-old) Ly9 (-/-) mice key cell subsets implicated in autoimmunity were expanded, e.g., T follicular helper (Tfh) as well as germinal center (GC) B cells. More importantly, in vitro functional experiments showed that Ly9 acts as an inhibitory receptor of IFN-? producing CD4(+) T cells. Taken together, our findings reveal that the Ly9 receptor triggers cell intrinsic safeguarding mechanisms to prevent a breach of tolerance, emerging as a new non-redundant inhibitory cell-surface receptor capable of disabling autoantibody responses.

SUBMITTER: de Salort J 

PROVIDER: S-EPMC3728625 | BioStudies | 2013-01-01T00:00:00Z

REPOSITORIES: biostudies

Similar Datasets

2018-01-01 | S-EPMC5762399 | BioStudies
1000-01-01 | S-EPMC4707085 | BioStudies
2013-01-01 | S-EPMC3531811 | BioStudies
2018-01-01 | S-EPMC6251324 | BioStudies
2015-01-01 | S-EPMC4610628 | BioStudies
2011-01-01 | S-EPMC3119727 | BioStudies
1000-01-01 | S-EPMC5835059 | BioStudies
2020-01-01 | S-EPMC7005855 | BioStudies
1000-01-01 | S-EPMC4564365 | BioStudies
2016-01-01 | S-EPMC5206809 | BioStudies