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Front. Immunol. | doi: 10.3389/fimmu.2018.02661

Ly9 (CD229) antibody targeting depletes marginal zone and germinal center B cells in lymphoid tissues and reduces salivary gland inflammation in a mouse model of Sjögren’s Syndrome

  • 1University of Barcelona, Spain
  • 2Centro Nacional de Investigaciones Oncológicas (CNIO), Spain

Sjögren’s Syndrome (SjS) is a common chronic autoimmune disease characterized by the B cell hyperactivation, lymphocyte infiltration and tissue damage of exocrine glands. It can also present life-threating extraglandular manifestations, such as pulmonary and hepatic involvement, renal inflammation and marginal zone (MZ) B cell lymphoma. Several biologic agents have been tested in SjS but none has shown significant efficacy. Here, we report the effects of Ly9 (CD229) antibody targeting, a cell surface molecule that belong to the SLAM family of immunomodulatory receptors, using NOD.H-2h4 mice as a model of SjS-like disease. Female mice were treated with anti-Ly9 antibody or isotype control at week 24, when all mice present SjS related autoantibodies, salivary gland infiltrates and marginal zone (MZ) B cell pool enlargement. Antibody injection depleted key lymphocyte subsets involved in SjS pathology such as MZ, B1 and germinal center B cells in spleen and draining lymph nodes without inducing a general immunosuppression. Importantly, mice receiving anti-Ly9 mAb showed a reduced lymphocyte infiltrate within salivary glands. This reduction may be, in part, explained by the down-regulation of L-selectin and alfa4/beta7 integrin induced by the anti-Ly9 antibody. Furthermore, levels of anti-nuclear autoantibodies were reduced after anti-Ly9 treatment. These data indicate that Ly9 is a potential therapeutic target for the treatment of SjS.

Keywords: Autoimmunity, Sjögren syndrome, antibody targeting, SLAM family of receptors, Ly9 (CD229/SLAMF3)

Received: 03 Aug 2018; Accepted: 29 Oct 2018.

Edited by:

Urs Christen, Goethe-Universität Frankfurt am Main, Germany

Reviewed by:

Kerstin Nundel, University of Massachusetts Medical School, United States
Keiko Yoshimoto, Keio University School of Medicine  

Copyright: © 2018 Puñet-Ortiz, Sáez Moya, Cuenca, Caleiras, Lázaro and Engel. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Pablo Engel, University of Barcelona, Barcelona, 08007, Catalonia, Spain, pengel@ub.edu