Cenerimod, a selective S1P1 receptor modulator, improves organ-specific disease outcomes in animal models of Sjögren’s syndrome

Abstract Background Sjögren’s syndrome is a systemic autoimmune disease characterized by immune cells predominantly infiltrating the exocrine glands and frequently forming ectopic lymphoid structures. These structures drive a local functional immune response culminating in autoantibody production an...

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Autores principales:	Estelle Gerossier, Saba Nayar, Sylvie Froidevaux, Charlotte G. Smith, Celine Runser, Valentina Iannizzotto, Enrico Vezzali, Gabin Pierlot, Ulrich Mentzel, Mark J. Murphy, Marianne M. Martinic, Francesca Barone
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Sjögren’s syndrome Sphingosine-1-phosphate receptor type 1 Animal models Immunomodulation Cenerimod Diseases of the musculoskeletal system RC925-935
Acceso en línea:	https://doaj.org/article/61ff86a6cb164b9daf9e959da2dde53e
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spelling	oai:doaj.org-article:61ff86a6cb164b9daf9e959da2dde53e2021-12-05T12:04:42ZCenerimod, a selective S1P1 receptor modulator, improves organ-specific disease outcomes in animal models of Sjögren’s syndrome10.1186/s13075-021-02673-x1478-6362https://doaj.org/article/61ff86a6cb164b9daf9e959da2dde53e2021-11-01T00:00:00Zhttps://doi.org/10.1186/s13075-021-02673-xhttps://doaj.org/toc/1478-6362Abstract Background Sjögren’s syndrome is a systemic autoimmune disease characterized by immune cells predominantly infiltrating the exocrine glands and frequently forming ectopic lymphoid structures. These structures drive a local functional immune response culminating in autoantibody production and tissue damage, associated with severe dryness of mucosal surfaces and salivary gland hypofunction. Cenerimod, a potent, selective and orally active sphingosine-1-phosphate receptor 1 modulator, inhibits the egress of lymphocytes into the circulation. Based on the mechanism of action of cenerimod, its efficacy was evaluated in two mouse models of Sjögren’s syndrome. Methods Cenerimod was administered in two established models of Sjögren’s syndrome; firstly, in an inducible acute viral sialadenitis model in C57BL/6 mice, and, secondly, in the spontaneous chronic sialadenitis MRL/lpr mouse model. The effects of cenerimod treatment were then evaluated by flow cytometry, immunohistochemistry, histopathology and immunoassays. Comparisons between groups were made using a Mann-Whitney test. Results In the viral sialadenitis model, cenerimod treatment reduced salivary gland immune infiltrates, leading to the disaggregation of ectopic lymphoid structures, reduced salivary gland inflammation and preserved organ function. In the MRL/lpr mouse model, cenerimod treatment decreased salivary gland inflammation and reduced T cells and proliferating plasma cells within salivary gland ectopic lymphoid structures, resulting in diminished disease-relevant autoantibodies within the salivary glands. Conclusions Taken together, these results suggest that cenerimod can reduce the overall autoimmune response and improve clinical parameters in the salivary glands in models of Sjögren’s syndrome and consequently may reduce histological and clinical parameters associated with the disease in patients.Estelle GerossierSaba NayarSylvie FroidevauxCharlotte G. SmithCeline RunserValentina IannizzottoEnrico VezzaliGabin PierlotUlrich MentzelMark J. MurphyMarianne M. MartinicFrancesca BaroneBMCarticleSjögren’s syndromeSphingosine-1-phosphate receptor type 1Animal modelsImmunomodulationCenerimodDiseases of the musculoskeletal systemRC925-935ENArthritis Research & Therapy, Vol 23, Iss 1, Pp 1-19 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Sjögren’s syndrome Sphingosine-1-phosphate receptor type 1 Animal models Immunomodulation Cenerimod Diseases of the musculoskeletal system RC925-935
spellingShingle	Sjögren’s syndrome Sphingosine-1-phosphate receptor type 1 Animal models Immunomodulation Cenerimod Diseases of the musculoskeletal system RC925-935 Estelle Gerossier Saba Nayar Sylvie Froidevaux Charlotte G. Smith Celine Runser Valentina Iannizzotto Enrico Vezzali Gabin Pierlot Ulrich Mentzel Mark J. Murphy Marianne M. Martinic Francesca Barone Cenerimod, a selective S1P1 receptor modulator, improves organ-specific disease outcomes in animal models of Sjögren’s syndrome
description	Abstract Background Sjögren’s syndrome is a systemic autoimmune disease characterized by immune cells predominantly infiltrating the exocrine glands and frequently forming ectopic lymphoid structures. These structures drive a local functional immune response culminating in autoantibody production and tissue damage, associated with severe dryness of mucosal surfaces and salivary gland hypofunction. Cenerimod, a potent, selective and orally active sphingosine-1-phosphate receptor 1 modulator, inhibits the egress of lymphocytes into the circulation. Based on the mechanism of action of cenerimod, its efficacy was evaluated in two mouse models of Sjögren’s syndrome. Methods Cenerimod was administered in two established models of Sjögren’s syndrome; firstly, in an inducible acute viral sialadenitis model in C57BL/6 mice, and, secondly, in the spontaneous chronic sialadenitis MRL/lpr mouse model. The effects of cenerimod treatment were then evaluated by flow cytometry, immunohistochemistry, histopathology and immunoassays. Comparisons between groups were made using a Mann-Whitney test. Results In the viral sialadenitis model, cenerimod treatment reduced salivary gland immune infiltrates, leading to the disaggregation of ectopic lymphoid structures, reduced salivary gland inflammation and preserved organ function. In the MRL/lpr mouse model, cenerimod treatment decreased salivary gland inflammation and reduced T cells and proliferating plasma cells within salivary gland ectopic lymphoid structures, resulting in diminished disease-relevant autoantibodies within the salivary glands. Conclusions Taken together, these results suggest that cenerimod can reduce the overall autoimmune response and improve clinical parameters in the salivary glands in models of Sjögren’s syndrome and consequently may reduce histological and clinical parameters associated with the disease in patients.
format	article
author	Estelle Gerossier Saba Nayar Sylvie Froidevaux Charlotte G. Smith Celine Runser Valentina Iannizzotto Enrico Vezzali Gabin Pierlot Ulrich Mentzel Mark J. Murphy Marianne M. Martinic Francesca Barone
author_facet	Estelle Gerossier Saba Nayar Sylvie Froidevaux Charlotte G. Smith Celine Runser Valentina Iannizzotto Enrico Vezzali Gabin Pierlot Ulrich Mentzel Mark J. Murphy Marianne M. Martinic Francesca Barone
author_sort	Estelle Gerossier
title	Cenerimod, a selective S1P1 receptor modulator, improves organ-specific disease outcomes in animal models of Sjögren’s syndrome
title_short	Cenerimod, a selective S1P1 receptor modulator, improves organ-specific disease outcomes in animal models of Sjögren’s syndrome
title_full	Cenerimod, a selective S1P1 receptor modulator, improves organ-specific disease outcomes in animal models of Sjögren’s syndrome
title_fullStr	Cenerimod, a selective S1P1 receptor modulator, improves organ-specific disease outcomes in animal models of Sjögren’s syndrome
title_full_unstemmed	Cenerimod, a selective S1P1 receptor modulator, improves organ-specific disease outcomes in animal models of Sjögren’s syndrome
title_sort	cenerimod, a selective s1p1 receptor modulator, improves organ-specific disease outcomes in animal models of sjögren’s syndrome
publisher	BMC
publishDate	2021
url	https://doaj.org/article/61ff86a6cb164b9daf9e959da2dde53e
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Cenerimod, a selective S1P1 receptor modulator, improves organ-specific disease outcomes in animal models of Sjögren’s syndrome

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