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.
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 September 19, 2019.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/tofacitinib-suppresses-lymphocytic-infiltration-in-the-salivary-gland-of-non-obese-diabetic-mice-the-animal-model-of-sjgrens-syndrome/