Salivary gland epithelial cells from patients with Sjögren's syndrome induce B-lymphocyte survival and activation.


Journal

Annals of the rheumatic diseases
ISSN: 1468-2060
Titre abrégé: Ann Rheum Dis
Pays: England
ID NLM: 0372355

Informations de publication

Date de publication:
11 2020
Historique:
received: 04 11 2019
revised: 09 07 2020
accepted: 10 07 2020
pubmed: 28 8 2020
medline: 15 12 2020
entrez: 27 8 2020
Statut: ppublish

Résumé

Primary Sjögren's syndrome (pSS) is characterised by chronic hyperactivation of B lymphocytes. Salivary gland epithelial cells (SGECs) could play a role in promoting B-lymphocyte activation within the target tissue. We aimed to study the interactions between SGECs from patients with pSS or controls and B lymphocytes. Patients had pSS according to 2016 European League Against Rheumatism/American College of Rheumatology criteria. Gene expression analysis of SGECs and B lymphocytes from pSS and controls isolated from salivary gland biopsies and blood was performed by RNA-seq. SGECs from pSS and controls were cocultured with B-lymphocytes sorted from healthy donor blood and were stimulated. Transwell and inhibition experiments were performed. Gene expression analysis of SGECs identified an upregulation of interferon signalling pathway and genes involved in immune responses ( SGECs from patients with pSS had better ability than those from controls to induce survival and activation of B lymphocytes. Targeting a single cytokine did not inhibit this effect, whereas leflunomide, BTK or PI3K inhibitors partially decreased B-lymphocyte viability in this model. This gives indications for future therapeutic options in pSS.

Identifiants

pubmed: 32843324
pii: annrheumdis-2019-216588
doi: 10.1136/annrheumdis-2019-216588
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1468-1477

Commentaires et corrections

Type : CommentIn
Type : CommentIn

Informations de copyright

© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.

Déclaration de conflit d'intérêts

Competing interests: AT, NA and MM are employed by Biogen. XM received an honorarium for consultancy advice on Sjögren’s syndrome from BMS, GSK, Novartis and Servier and a research grant from Servier. The rest of the authors declare that they have no relevant conflicts of interest.

Auteurs

Elodie Rivière (E)

Immunology of viral Infections and Autoimmune Diseases, IDMIT, CEA, Paris-Saclay University, Paris-Sud University, INSERM U1184, Le Kremlin-Bicêtre, France.
Fondation Arthritis, Arthritis R&D, Paris, France.
Rheumatology, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpitaux universitaires Paris-Sud, Hôpital Bicêtre, Le Kremlin Bicêtre, France.

Juliette Pascaud (J)

Immunology of viral Infections and Autoimmune Diseases, IDMIT, CEA, Paris-Saclay University, Paris-Sud University, INSERM U1184, Le Kremlin-Bicêtre, France.

Nicolas Tchitchek (N)

Immunology of viral Infections and Autoimmune Diseases, IDMIT, CEA, Paris-Saclay University, Paris-Sud University, INSERM U1184, Le Kremlin-Bicêtre, France.

Saida Boudaoud (S)

Immunology of viral Infections and Autoimmune Diseases, IDMIT, CEA, Paris-Saclay University, Paris-Sud University, INSERM U1184, Le Kremlin-Bicêtre, France.

Audrey Paoletti (A)

Immunology of viral Infections and Autoimmune Diseases, IDMIT, CEA, Paris-Saclay University, Paris-Sud University, INSERM U1184, Le Kremlin-Bicêtre, France.

Bineta Ly (B)

Immunology of viral Infections and Autoimmune Diseases, IDMIT, CEA, Paris-Saclay University, Paris-Sud University, INSERM U1184, Le Kremlin-Bicêtre, France.

Anastasia Dupré (A)

Immunology of viral Infections and Autoimmune Diseases, IDMIT, CEA, Paris-Saclay University, Paris-Sud University, INSERM U1184, Le Kremlin-Bicêtre, France.

Hua Chen (H)

Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Beijing, China.

Alice Thai (A)

Immunology Research, Biogen, Cambridge, Massachusetts, USA.

Norm Allaire (N)

Immunology Research, Biogen, Cambridge, Massachusetts, USA.

Bernd Jagla (B)

Biomarker Discovery Platform UTechS CB, Hub de Bioinformatique et biostatistique C3IB, Institut Pasteur, Paris, France.

Michael Mingueneau (M)

Immunology Research, Biogen, Cambridge, Massachusetts, USA.

Gaetane Nocturne (G)

Immunology of viral Infections and Autoimmune Diseases, IDMIT, CEA, Paris-Saclay University, Paris-Sud University, INSERM U1184, Le Kremlin-Bicêtre, France gaetane.nocturne@aphp.fr.
Rheumatology, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpitaux universitaires Paris-Sud, Hôpital Bicêtre, Le Kremlin Bicêtre, France.

Xavier Mariette (X)

Immunology of viral Infections and Autoimmune Diseases, IDMIT, CEA, Paris-Saclay University, Paris-Sud University, INSERM U1184, Le Kremlin-Bicêtre, France.
Rheumatology, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpitaux universitaires Paris-Sud, Hôpital Bicêtre, Le Kremlin Bicêtre, France.

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