Gene expression analysis of T cell subsets infiltrating lacrimal glands from the NOD mouse model of Sjögren's. Mus musculus

Despite being one of the most common rheumatologic diseases, there is still no disease-modifying drug for primary Sjögren’s syndrome (pSS). Advancing our knowledge of the target tissue has been limited by the low dimensionality of histology techniques and the small size of human salivary gland biopsies. The goal of this study was to characterize CD4+ T cell subsets infiltrating the target tissue of the disease. We took advantage of a molecularly-validated mouse model of pSS (the NOD mouse model) and used cytometry techniques (flow and mass cytometry) in combination with transcriptional analyses. We identified three novel CD4+ T cell subsets that were not previously described in pSS pathogenesis and this GEO dataset reports the transcriptomic analysis of each of these three subsets: (1) effector Tregs (eTregs) expressing high levels of PD1 and ICOS as well as many immunoregulatory factors such as Il10, Areg, Fgl2, Itgb8; (2) Il21+ Th1 cells that also expressed high levels of PD1 and ICOS as well as osteopontin and shared striking transcriptional similarities with a pathogenic T follicular subset described in several lupus mouse models; (3) naïve PD1neg ICOSneg CD4+ T cells. Overall design: All three T-cell subsets were purified from lacrimal gland (LG) cell suspensions of 16-week old male NOD mice by FACS cell sorting (>99% purity) using the following surface markers: TCRbeta, CD4, PD1, ICOS, CD73, CD200, and the DAPI as live/dead dye. The PD1negICOSneg population (naive) was isolated as DAPI-CD4+TCRb+PD1-ICOS-; the effector Treg (eTreg) population was isolated as DAPI-CD4+TCRb+PD1highICOShighCD73lowCD200low; the effector Tconv (eTconv) population was isolated as DAPI-CD4+TCRb+PD1highICOShighCD73lowCD200low;RNA was purified and QC’d before processing for gene expression analysis. Total CD4+ and CD8+ T cells from the spleen of the same mice as controls.