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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.
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https://www.hal.inserm.fr/inserm-03150054
Contributor : Elodie Riviere <>
Submitted on : Tuesday, February 23, 2021 - 2:46:00 PM
Last modification on : Wednesday, June 23, 2021 - 2:18:12 PM
Long-term archiving on: : Monday, May 24, 2021 - 8:24:05 PM

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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⟩

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