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Title:
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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
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Author:
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Puñet Ortiz, Joan; Sáez Moya, Manuel; Cuenca, Marta; Caleiras, Eduardo; Lázaro, Adriana; Engel Rocamora, Pablo
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Notes:
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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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Subject(s):
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-Autoimmunitat
-Síndrome de Sjögren
-Models animals en la investigació
-Autoimmunity
-Sjogren's syndrome
-Animal models in research |
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Rights:
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cc-by (c) Puñet Ortiz, Joan et al., 2018
http://creativecommons.org/licenses/by/3.0/es
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Document type:
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Article
Article - Published version |
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Published by:
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Frontiers Media
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