Inhibition of JAK-STAT pathway corrects salivary gland inflammation and interferon driven immune activation in Sjogren's Disease.

ABSTRACT:

Objectives

Inflammatory cytokines that signal through the JAK- STAT pathway, especially interferons (IFNs), are implicated in Sjögren's Disease (SjD). Although inhibition of JAKs is effective in other autoimmune diseases, a systematic investigation of IFN-JAK-STAT signaling and effect of JAK inhibitor (JAKi) therapy in SjD-affected human tissues has not been reported.

Methods

Human minor salivary glands (MSGs) and peripheral blood mononuclear cells (PBMCs) were investigated using bulk or single cell (sc) RNA sequencing (RNAseq), immunofluorescence microscopy (IF), and flow cytometry. Ex vivo culture assays on PBMCs and primary salivary gland epithelial cell (pSGEC) lines were performed to model changes in target tissues before and after JAKi.

Results

RNAseq and

SUBMITTER: Gupta S 

PROVIDER: S-EPMC10473773 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature