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THU0264 A Selective JAK1 Inhibitor, Filgotinib Suppresses Lymphocytic Infiltration in Salivary Gland of Non Obese Diabetic Mice via Suppression of Baff Production of Salivary Gland Epithelial Cells
  1. J. Lee1,
  2. J. Lee2,
  3. S.-Y. Baek2,
  4. J.H. Koh1,
  5. M.-K. Chung1,
  6. H. Jeon1,
  7. S.H. Kim1,
  8. J.H. Yoo1,
  9. H. Kim1,
  10. S.-K. Kwok1,
  11. J.H. Ju1,
  12. S.-H. Park1
  1. 1Division of Rheumatology, Department of Internal Medicine, School of Medicine, The Catholic University of Korea, Seoul St. Mary's Hospital
  2. 2Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, Korea, Republic Of

Abstract

Background Interferon (IFN) signatures are upregulated in patients with primary Sjogren's syndrome (pSS) and interferons are considered to play a pathogenic role in pSS. Therefore, Janus kinase (JAK) which mediates interferon signaling pathway may be a good therapeutic target

Objectives We set out to investigate whether a selective JAK1 inhibitor, filgotinib would ameliorate disease-related parameters in non-obese diabetic (NOD) mice, an animal model SS

Methods Filgotinib (1.5mg/kg) or vehicle (saline) was intraperitoneally injected three times per week from 8 weeks after birth. Salivary flow rate (SFR) was addressed on 8, 12, 16 and 20 weeks. Histologic analysis was performed on 20 weeks. The effect of filgotinib on the expressions of B cell activating factor (BAFF) and chemokines (CXCL10 [IP-10], CXCL3 [fractalkine], CCL-2 [MCP-1]) in human salivary gland epithelial cell (SGEC) line or primary epithelial cells of patients with pSS was determined in vitro.

Results The SFR of NOD mice in both groups decreased over time. Of note, SFRs of filgotinib-treated mice were greater than those of controls. Histologic evaluation of the salivary gland revealed that the lymphocytic infiltration of salivary gland was markedly reduced in the mice treated with filgotinib. Filgotinib suppressed STAT1 phosphorylation in IFN-treated SGECs. In addition, IFN-induced BAFF and chemokine production of SGECs or primary epithelial cells were abrogated by filgotinib treatment.

Conclusions Filgotinib suppresses SFR decrease and lymphocytic infiltration of salivary glands of NOD mice by inhibiting inhibiting IFN signaling pathway, thus suppressing BAFF and chemokine production of salivary gland epithelial cells. JAK inhibition may be a novel therapeutic approach for SS.

Disclosure of Interest None declared

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