Frontiers in Immunology (Jul 2013)
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-ANA, -dsDNA and -nucleosome autoantibodies, independently of genetic background ([B6.129] or [BALB/c.129]). In aged [10-12 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-g 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.
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