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Title: 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
Author: Puñet Ortiz, Joan
Sáez Moya, Manuel
Cuenca, Marta
Caleiras, Eduardo
Lázaro, Adriana
Engel Rocamora, Pablo
Keywords: Autoimmunitat
Síndrome de Sjögren
Models animals en la investigació
Sjogren's syndrome
Animal models in research
Issue Date: 16-Nov-2018
Publisher: Frontiers Media
Abstract: 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-threatening 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 belongs 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.
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It is part of: Frontiers in Immunology, 2018, vol. 9, p. 2661
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ISSN: 1664-3224
Appears in Collections:Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Biomedicina)

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