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

• Published in: Oral science international Vol. 21; no. 3; pp. 415 - 424
• Main Authors: Aota, Keiko, Kani, Koichi, Ono, Shinji, Naniwa, Kohei, Momota, Yukihiro, Fukui, Makoto, Ishimaru, Naozumi, Azuma, Masayuki
• Format: Journal Article
• Language: English
• Published: 01.09.2024
• Subjects: autoimmunity; JAK1; JAK2; labial salivary gland; Sjögren's syndrome
• ISSN: 1348-8643; 1881-4204
• DOI: 10.1002/osi2.1241

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.