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

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 inflam...

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Autores: Puñet Ortiz, Joan, Sáez Moya, Manuel, Cuenca, Marta, Caleiras, Eduardo, Lázaro Palacios, Ariadna, Engel Rocamora, Pablo
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2018
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/146483
Acceso en línea:https://hdl.handle.net/2445/146483
Access Level:acceso abierto
Palabra clave:Autoimmunitat
Síndrome de Sjögren
Models animals en la investigació
Autoimmunity
Sjogren's syndrome
Animal models in research
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spelling 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 SyndromePuñet Ortiz, JoanSáez Moya, ManuelCuenca, MartaCaleiras, EduardoLázaro Palacios, AriadnaEngel Rocamora, PabloAutoimmunitatSíndrome de SjögrenModels animals en la investigacióAutoimmunitySjogren's syndromeAnimal models in researchSjögren'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.Frontiers Media2018info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/146483Articles publicats en revistes (Biomedicina)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.3389/fimmu.2018.02661Frontiers in Immunology, 2018, vol. 9, p. 2661https://doi.org/10.3389/fimmu.2018.02661cc-by (c) Puñet Ortiz, Joan et al., 2018http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1464832026-05-27T06:46:51Z
dc.title.none.fl_str_mv 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
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
spellingShingle 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
Puñet Ortiz, Joan
Autoimmunitat
Síndrome de Sjögren
Models animals en la investigació
Autoimmunity
Sjogren's syndrome
Animal models in research
title_short 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_sort 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
dc.creator.none.fl_str_mv Puñet Ortiz, Joan
Sáez Moya, Manuel
Cuenca, Marta
Caleiras, Eduardo
Lázaro Palacios, Ariadna
Engel Rocamora, Pablo
author Puñet Ortiz, Joan
author_facet Puñet Ortiz, Joan
Sáez Moya, Manuel
Cuenca, Marta
Caleiras, Eduardo
Lázaro Palacios, Ariadna
Engel Rocamora, Pablo
author_role author
author2 Sáez Moya, Manuel
Cuenca, Marta
Caleiras, Eduardo
Lázaro Palacios, Ariadna
Engel Rocamora, Pablo
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Autoimmunitat
Síndrome de Sjögren
Models animals en la investigació
Autoimmunity
Sjogren's syndrome
Animal models in research
topic Autoimmunitat
Síndrome de Sjögren
Models animals en la investigació
Autoimmunity
Sjogren's syndrome
Animal models in research
description 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.
publishDate 2018
dc.date.none.fl_str_mv 2018
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/146483
url https://hdl.handle.net/2445/146483
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.3389/fimmu.2018.02661
Frontiers in Immunology, 2018, vol. 9, p. 2661
https://doi.org/10.3389/fimmu.2018.02661
dc.rights.none.fl_str_mv cc-by (c) Puñet Ortiz, Joan et al., 2018
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Puñet Ortiz, Joan et al., 2018
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv Articles publicats en revistes (Biomedicina)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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