2026-06-14T03:54:59Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/83542024-11-29T18:34:51Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Puñet-Ortiz, Joan author Sáez Moya, Manuel author Cuenca, Marta author Caleiras, E author Lazaro, Adriana author Engel, Pablo author 2018-11-16 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. Front Immunol. 2018;9:2661. 10.3389/fimmu.2018.02661 1664-3224 1664-3224 Frontiers in immunology 30519241 http://hdl.handle.net/20.500.12105/8354 Ly9 SLAM family receptors Sjögren's Syndrome Antibody targeting Autoimmunity 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