Tofacitinib Suppresses Lymphocytic Infiltration in the Salivary Gland of Non-Obese Diabetic Mice; The Animal Model of Sjögren's Syndrome

Jennifer Lee¹, Ji Yeon Lee², Jung Hee Koh³, Min Kyung Chung⁴, Ji Hun Kim¹, Seung-Ki Kwok⁵, Ji Hyeon Ju² and Sung-Hwan Park⁶, ¹Division of Rheumatology, Department of Internal Medicine, College of Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, South Korea, ²Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea, ³Division of Rheumatology, Department of Internal Medicine, School of Medicine, The Catholic University of Korea, Seoul St. Mary's Hospital, Seoul, South Korea, ⁴Division of Rheumatology, Department of Internal Medicine, School of Medicine, The Catholic University of Korea, Seoul St. Mary’s Hospital, Seoul, South Korea, ⁵[email protected], Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea, ⁶Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, Seoul, South Korea

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: animal models and tofacitinib, Janus kinase (JAK), Sjogren's syndrome

Session Information

Date: Tuesday, November 10, 2015

Title: Sjögren's Syndrome: Translational Insights into Sjögren's Syndrome

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose: Interferon signatures are upregulated in patients with primary Sjogren’s syndrome (pSS) and interferons are considered to have a pathogenic role in pSS. As Janus kinase (JAK) mediates interferon signaling pathway, we investigated whether tofacitinib would ameliorate disease-related parameters in non-obese diabetic (NOD) mice, the animal model SS.

Methods: Tofacitinib (1.5mg/kg or 15mg/kg) or vehicle (10% DMSO) was intraperitoneally injected twice per week from 8 weeks after birth. Salivary flow rate (SFR) and serum level of immunoglobulin(Ig) were addressed on 8 weeks, 12 weeks and 16 weeks. Histologic analysis was performed on 16 weeks. Various T and B cell subpopulations were evaluated using FACS and RT PCR with ex vivo splenocytes and cervical lymph node cells.

Results: The SFR of NOD mice all three groups decreased over time. On 16 weeks, the salivary flow rates of tofacitinib-treated mice were higher than those of controls. Serum level of IgM was also lower in tofacitinib-treated mice on 16 weeks. Histologic evaluation of the salivary gland revealed that the lymphocytic infiltration of salivary gland was markedly reduced in the mice treated with tofacitinib. Tofacitinib suppressed Th1 differentiation in vitro and the expression of B cell activation markers (Bcl-6, AID) was lower in ex vivo B cells of tofacitinib-treated mice compared with controls.

Conclusion: Tofacitinib suppressed lymphocytic infiltration in the salivary gland of NOD mice, which suggests the therapeutic potential of tofacitinib in pSS.

Disclosure: J. Lee, None; J. Y. Lee, None; J. H. Koh, None; M. K. Chung, None; J. H. Kim, None; S. K. Kwok, None; J. H. Ju, None; S. H. Park, None.

To cite this abstract in AMA style:

Lee J, Lee JY, Koh JH, Chung MK, Kim JH, Kwok SK, Ju JH, Park SH. Tofacitinib Suppresses Lymphocytic Infiltration in the Salivary Gland of Non-Obese Diabetic Mice; The Animal Model of Sjögren’s Syndrome [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/tofacitinib-suppresses-lymphocytic-infiltration-in-the-salivary-gland-of-non-obese-diabetic-mice-the-animal-model-of-sjgrens-syndrome/. Accessed .

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