4.8 Article

Ly9 (CD229) cell-surface receptor is crucial for the development of spontaneous autoantibody produc on to nuclear antigens

Journal

FRONTIERS IN IMMUNOLOGY
Volume 4, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2013.00225

Keywords

SLAMF; Ly9 (CD229, SLAMF3); anti-DNA autoantibodies; disease susceptibility; systemic lupus erythematosus; murine Lupus

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Funding

  1. Ministerio de Educacion y Ciencia [SAF 2009-07071/SAF 2012-39536]
  2. NIH [2P01AI65687-06A1]
  3. Ayuda Personal Investigador en Formacion (APIF)
  4. Universitat de Barcelona. Marta Cuenca
  5. Ministerio de Educacion, Cultura y Deporte [AP2010-1754]
  6. Beatriu de Pinos [2010 BP-B]

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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 1(86.129) 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-gamma producing CDR+ 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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