Among this gene set, regulation of T cell activation (p=4.06×10<sup>-7</sup>) and T cell receptor (TCR) signalling pathway (p=1.73×10<sup>-6</sup>) were particularly concentrated, including <i>PTPRC</i> (<i>CD45</i>), <i>LCK</i>, <i>LAT-SLP76</i> complex genes (<i>THEMIS</i>, <i>LAT</i>, <i>ITK</i>, <i>TEC</i>, <i>TESPA1</i>, <i>PLCL1)</i>, <i>DGKD</i>, <i>PRKD1</i>, <i>PAK2</i> and <i>NFAT5</i>, shared across 14 SLE, RA and pSS families.
CCL25, CXCL10, CCL17, CCL20 and CCL27 mRNA and protein expression of salivary gland tissue of pSS and non-Sjögren's sicca (non-SS) patients was assessed.
CCR9 + T helper (Th) cells can induce Sjögren-like symptoms in mice and both CCR9 + Th cells and their ligand CCL25 are increased in the salivary glands of primary Sjögren's syndrome (pSS) patients.
These data demonstrate activation of PI3Kδ pathway within the glands of patients with pSS and its contribution to disease pathogenesis in a model of disease, supporting the exploration of the therapeutic potential of PI3Kδ pathway inhibition in this condition.
To investigate the differential expression of miR-17-92 cluster, which encodes 6 microRNAs (miR-NAs) including miR-17, miR-18a, miR-19a, miR-19b, miR-20a and miR-92a, among varying histological stages of labial minor salivary gland (MSG) tis- sues in patients with primary Sjögren's syndrome (pSS).
<b>Conclusions:</b> The decreased expression of miR-130a and miR-708 in pSS cDC2s seems to reflect cell activation. miR-130a targets MSK1, which regulates pro-inflammatory cytokine production, and we provide proof-of-concept for MSK1-inhibition as a therapeutic avenue to impede cDC2 activity in pSS.
The cysteine protease cathepsin S (CatS) is crucially involved in MHCII processing and T cell stimulation, and elevated levels have been found in patients with RA, psoriasis and pSS.
We undertook the present study to delineate the function of CXorf21 in the immune system as well as investigate a potential role in the sex bias of SLE and pSS.
Herein, we investigated the expression and effect of second mitochondria-derived activator of caspase (Smac) in patients with pSS and associated the expression with clinicopathological parameters.
<b>Conclusions:</b> The decreased expression of miR-130a and miR-708 in pSS cDC2s seems to reflect cell activation. miR-130a targets MSK1, which regulates pro-inflammatory cytokine production, and we provide proof-of-concept for MSK1-inhibition as a therapeutic avenue to impede cDC2 activity in pSS.
In this setting, cytokine production was associated with expression of hub-genes from the IFN-induced and ribosomal protein gene-signatures, indicating that the transcriptional profile of pSS pDCs underlies their enhanced cytokine production.
Target validation assays showed significant expression of phosphorylated ribosomal protein S6 (pS6), a downstream mediator of the phosphatidylinositol 3-kinase delta (PI3Kδ) pathway, within pSS salivary glands. pS6 distribution was found to co-localise with T/B cell markers within pSS aggregates and the CD138+ plasma cells infiltrating the glands.
In this study, we present data demonstrating a negative correlation of the epithelial marker E-cadherin expression and a positive correlation of mesenchymal vimentin and collagen type I expression with increasing degrees of tissue inflammation in pSS SG specimens.