シェーグレン症候群新規治療薬としてのJAK阻害薬の可能性

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  • JAK inhibitors as a potential therapeutic agents for Sjögren’s syndrome

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Sjögren’s syndrome (SS) is a chronic autoimmune disease involving the salivary and lacrimal glands. Expression of interferon (IFN)-related molecules and C-X-C motif chemokine ligand 10 (CXCL10) is upregulated in labial salivary glands (LSGs) of patients with primary SS (pSS). CXCL10 plays a role in SS pathogenesis via immune-cell accumulation. In various inflammatory diseases, including pSS, the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway is activated; moreover, in pSS, the JAK/STAT pathway is associated with CXCL10 production in the LSG tissues. Here, we evaluated potential JAK inhibitor, Baricitinib, as therapeutic agents for pSS by analyzing LSGs of patients with pSS and immortalized normal human salivary gland cell lines, namely NS-SV-DC, and NS-SV-AC. Immunohistochemical analysis revealed strong expression of phosphorylated JAK1 and JAK2 in the ductal epithelial cells of LSGs of patients with pSS. Additionally, phosphorylated JAK2 was observed in several immune cells infiltrating around the ductal epithelium. Baricitinib, a selective JAK1/2 inhibitor, significantly inhibited IFN-γ-induced CXCL10 expression as well as CXCL10 protein levels in an immortalized normal human salivary gland ductal cell (NS-SV-DC) line. Additionally, western blotting showed that baricitinib suppressed the IFN-γ-induced phosphorylation of STAT1 and STAT3. In this review, based on these aforementioned fi ndings, we discussed the potential of JAK inhibitors as new therapeutic agents for pSS. JAK inhibitors may be useful in the treatment of patients with pSS.

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