ARTHRITIS & RHEUMATOLOGY | OCTOBER 15, 2020

Rivière E, Pascaud J, Virone A, Dupré A, Ly B, Paoletti A, Seror R, Tchitchek N, Mingueneau M, Smith N, Duffy D, Cassard L, Chaput N, Pengam S, Gauttier V, Poirier N, Mariette X and Nocturne G.

Arthritis Rheumatol. 2020 Oct 15

DOI: https://doi.org/10.1002/art.41558

ABSTRACT

OBJECTIVE

Primary Sjögren’s syndrome (pSS) is characterized by a lymphocytic infiltration of salivary glands and the presence of an interferon (IFN) signature. Salivary gland epithelial cells (SGECs) play an active role in pSS pathophysiology. The aim of this work was to study the interactions between SGECs and T cells in pSS and the role of the IL‐7/IFN axis.

METHODS

Primary cultured SGECs from pSS and controls were stimulated with poly(I:C), IFNα or IFNγ. T cells were sorted from blood and stimulated with IL‐7. CD25 expression was assessed by flow cytometry. Salivary gland explants were cultured for 4 days with anti‐IL‐7R antagonist antibody (OSE‐127) and transcriptomic analysis was performed by using nanostring.

RESULTS

IL‐7 serum level was increased in pSS patients versus controls and was associated with B‐cell biomarkers. IL7R expression was decreased in T cells from pSS patients versus controls. SGECs stimulated with poly(I:C), IFNα, or IFNγ secreted IL‐7. IL‐7 stimulation increased the activation of T cells, as well as IFNγ secretion. Transcriptomic analysis of salivary gland explants showed a correlation between IL7 and IFN expression. Lastly, explants cultured with anti‐IL‐7R antibody showed decreased IFN‐stimulated gene expression.

CONCLUSION

These results suggest an IL‐7‐IFNγ amplification loop involving SGECs and T cells in pSS. IL‐7 was secreted by SGECs stimulated with type 1 or type 2 IFN and, in turn, activate T cells that secrete type 2 IFN. An anti‐IL‐7R antibody decreased the IFN signature in T cells during pSS and could be of therapeutic interest.