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-γ 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.

journal_name

Front Immunol

journal_title

Frontiers in immunology

authors

de Salort J,Cuenca M,Terhorst C,Engel P,Romero X

doi

10.3389/fimmu.2013.00225

subject

Has Abstract

pub_date

2013-07-31 00:00:00

pages

225

issn

1664-3224

journal_volume

4

pub_type

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