Activation of Janus kinase 2 contributes to the autoimmune pathology in the salivary glands of patients with Sjögren's syndrome

Aim: Primary Sjögren's syndrome (pSS) is a chronic autoimmune disease that affects exocrine glands. CXCL10 production from salivary gland ductal cells via the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway has been suggested to be involved in glandular inflammation in pSS. We aimed to investigate JAK1, JAK2, phosphorylated JAK1, and phosphorylated JAK2 expression in labial salivary gland (LSG) tissues from patients with pSS to evaluate the potential of JAK inhibitors as therapeutic agents for pSS.
Methods: Immunohistochemical analysis was performed using LSG tissues of patients with pSS (n = 10), non-SS patients (n = 5), and healthy controls (n = 5). The LSG sections were scored to determine the expression levels of JAK1, JAK2, phosphorylated JAK1, and phosphorylated JAK2 in the ductal and acinar epithelium.
Results: In acinar epithelial cells of LSG tissues, JAK1, JAK2, and phosphorylated JAK1 expression was significantly lower in patients with pSS than in the controls. Significantly high expression of phosphorylated JAK1 and phosphorylated JAK2 was observed in the ductal epithelial cells of patients with pSS. However, there was no significant association between phosphorylated JAK1 or JAK2 expression levels and inflammation degree. Furthermore, immunofluorescence analysis revealed JAK2 phosphorylation in many CD3+ T cells infiltrating the LSG tissues.
Conclusions: The results suggest JAK2 activation in both ductal epithelial cells and infiltrating CD3+ T cells in LSG tissues of patients with pSS. JAK inhibitors may be effective therapeutic agents for pSS by regulating both chemokine production from salivary gland cells and effector T cell activation.

論文本文は2025-04-18以降公開予定

This is the peer reviewed version of the following article: Keiko Aota, Koichi Kani, Shinji Ono, Kohei Naniwa, Yukihiro Momota, Makoto Fukui, Naozumi Ishimaru, Masayuki Azuma, Activation of Janus kinase 2 contributes to the autoimmune pathology in the salivary glands of patients with Sjögren's syndrome. Oral Science International. 21, 3, 415-424, which has been published in final form at https://doi.org/10.1002/osi2.1241. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.