A Selective JAK1 Inhibitor, Filgotinib Suppresses Lymphocytic Infiltration in Salivary Gland of Non Obese Diabetic Mice Via Suppression of BAFF and Chemokine Production of Salivary Gland Epithelial Cells

Jennifer Lee¹, Seo Hwa Kim², Haneul Kim³, Seung-Ki Kwok⁴, Ji Hyeon Ju⁵ and Sung-Hwan Park⁵, ¹Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea, Republic of, ²Division of Rheumatology,, Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea, The Republic of, ³Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea, The Republic of, ⁴[email protected], Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea, ⁵Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: BAFF, Janus kinase (JAK), Sjogren's syndrome and interferons

Session Information

Date: Tuesday, November 15, 2016

Title: Sjögren's Syndrome I: Clinical Insights

Session Type: ACR Concurrent Abstract Session

Session Time: 2:30PM-4:00PM

Background/Purpose: 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. 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), IFN signature genes 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.

Conclusion: 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: J. Lee, None; S. H. Kim, None; H. Kim, None; S. K. Kwok, None; J. H. Ju, None; S. H. Park, None.

To cite this abstract in AMA style:

Lee J, Kim SH, Kim H, Kwok SK, Ju JH, Park SH. A Selective JAK1 Inhibitor, Filgotinib Suppresses Lymphocytic Infiltration in Salivary Gland of Non Obese Diabetic Mice Via Suppression of BAFF and Chemokine Production of Salivary Gland Epithelial Cells [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/a-selective-jak1-inhibitor-filgotinib-suppresses-lymphocytic-infiltration-in-salivary-gland-of-non-obese-diabetic-mice-via-suppression-of-baff-and-chemokine-production-of-salivary-gland-epithelial-ce/. Accessed .

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