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 Sjogren's Syndrome

被引：10

作者：

Punet-Ortiz, Joan ^{[1
]}

Saez Moya, Manuel ^{[1
]}

Cuenca, Marta ^{[1
]}

Caleiras, Eduardo ^{[2
]}

Lazaro, Adriana ^{[1
]}

Engel, Pablo ^{[1
,3
]}

机构：

[1] Univ Barcelona, Sch Med, Dept Biomed Sci, Immunol Unit, Barcelona, Spain

[2] Spanish Natl Canc Ctr CNIO, Biotechnol Program, Histopathol Unit, Madrid, Spain

[3] Inst Invest Biomed August Pi & Sunyer, Barcelona, Spain

来源：

FRONTIERS IN IMMUNOLOGY | 2018年 / 9卷

关键词：

autoimmunity; Sjogren's Syndrome; antibody targeting; SLAM family receptors; Ly9; LINKED LYMPHOPROLIFERATIVE DISEASE; SYNDROME CLINICAL PHENOTYPES; SLAM FAMILY; AUTOIMMUNE-DISEASES; ANIMAL-MODEL; MECHANISMS; MICE; ACTIVATION; EXPRESSION; RECEPTORS;

D O I：

10.3389/fimmu.2018.02661

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Sjogren'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-2(h4) 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.

引用

页数：14