Skip to Main content Skip to Navigation
Journal articles

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

Abstract : Objectives: Primary Sjögren's syndrome (pSS) is characterized by chronic hyperactivation of Blymphocytes. Salivary gland epithelial cells (SGECs) could play a role in promoting Blymphocyte activation within the target tissue. We aimed to study the interactions between SGECs from pSS patients or controls and B-lymphocytes. Methods: Patients had pSS according to 2016 EULAR/ACR 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 co-cultured with Blymphocytes sorted from healthy donor blood and stimulated. Transwell and inhibition experiments were performed. Results: Gene expression analysis of SGECs identified an upregulation of interferon signaling pathway and genes involved in immune responses (HLA-DRA, IL7, BAFFR) in pSS. Activation genes CD40 and CD48 were upregulated in salivary gland sorted B-lymphocytes from pSS patients. SGECs induced an increase in B-lymphocyte survival, which was higher for SGECs from pSS patients than controls. Moreover, when stimulated with Poly(I:C), SGECs from pSS patients induced higher activation of B-lymphocytes than those from controls. This effect depended on soluble factors. Inhibition with anti-BAFF, anti-APRIL, anti-IL6-R antibodies JAK1/3 inhibitor, or hydroxychloroquine had no effect, conversely to leflunomide, BTK or PI3K inhibitors. Conclusions: 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-lymphocytes viability in this model. This gives indications for future therapeutic options in pSS.
Document type :
Journal articles
Complete list of metadatas

https://www.hal.inserm.fr/inserm-03150054
Contributor : Elodie Riviere <>
Submitted on : Tuesday, February 23, 2021 - 2:46:00 PM
Last modification on : Thursday, February 25, 2021 - 3:26:46 AM

File

Salivary gland epithelial cell...
Files produced by the author(s)

Identifiers

Collections

Citation

Elodie Riviere, Juliette Pascaud, Nicolas Tchitchek, Saida Boudaoud, Audrey Paoletti, et al.. Salivary gland epithelial cells from patients with Sjögren's syndrome induce B-lymphocyte survival and activation. Annals of the Rheumatic Diseases, BMJ Publishing Group, 2020, 79 (11), pp.1468-1477. ⟨10.1136/annrheumdis-2019-216588⟩. ⟨inserm-03150054⟩

Share

Metrics

Record views

45

Files downloads

21