Project description:This study evaluated transcriptomic differences in cells with high and low expression of SLAMF7 in monocyte populations from blood and synovial fluid.
Project description:This study evaluated transcriptomic changes in monocyte-derived macrophages from healthy donors after stimulation with recombinant SLAMF7 or anti-SLAMF7 antibody, compared to macrophages without additional stimulation.
Project description:Long-term control of viral replication relies on the efficient differentiation of memory T cells into effector T cells during secondary immune responses. Recent findings have identified T cell precursors for both memory and exhausted T cells, suggesting the existence of progenitor-like effector T cells. These cells can persist without antigenic challenge but expand and acquire effector functions upon recall immune responses. In this study, we demonstrate that the combination of SLAMF7 with either CD27 or TCF-1 effectively identifies progenitor-like effector CD8 T cells, while SLAMF7 with GPR56 and TOX defines effector CD8 T cells. These markers allow for the clear segregation of these distinct cell subsets. SLAMF7+ CD8T cells are dynamically modulated during viral infections, including HIV, HCV, CMV, and SARS-CoV-2, as well as during aging. We further characterize the SLAMF7 signature at both phenotypic and transcriptional levels. Notably, during aging, the SLAMF7 pathway becomes dysregulated, resulting in persistent phosphorylation of STAT1. Additionally, SLAMF7 ligation in the presence of IL-15 induces TCF-1 expression, which promotes the homeostatic proliferation of progenitor-like effector CD8 T cells.
Project description:Comparison of circulating monocytes from pre- and postmanopausal females with low or high bone mineral density (BMD). Circulating monocytes are progenitors of osteoclasts, and produce factors important to bone metabolism. Results provide insight into the role of monocytes in osteoporosis. We identify osteoporosis genes by microarray analyses of monocytes in high vs. low hip BMD (bone mineral density) subjects.
Project description:Comparison of circulating monocytes from pre- and postmanopausal females with low or high bone mineral density (BMD). Circulating monocytes are progenitors of osteoclasts, and produce factors important to bone metabolism. Results provide insight into the role of monocytes in osteoporosis. We identify osteoporosis genes by microarray analyses of monocytes in high vs. low hip BMD (bone mineral density) subjects. Microarray analyses of monocytes were performed using Affymetrix HG-133A arrays in 80 Caucasian females, including 40 high (20 pre- and 20 postmanopausal) and 40 low hip BMD (20 pre- and 20 postmanopausal) subjects
Project description:Comparison of circulating monocytes from pre- and postmenopausal females with low or high bone mineral density (BMD). Circulating monocytes are progenitors of osteoclasts, and produce factors important to bone metabolism. Results provide insight into the role of monocytes in osteoporosis. We identify osteoporosis genes by microarray analyses of monocytes in high vs. low hip BMD (bone mineral density) subjects.
Project description:ATAC sequencing of primary human monocytes cultured at low and high density. Monocytes isolated from PBMCs of 3 healthy donors were cultured at low density (1 x 10^6 cells/mL) or at high density (1 x10^7 cells/mL) for 24hrs and harvested for ATAC sequencing. Protein expression of FcgR2b is higher on monocytes in high density conditions compared to low density conditions, where expression is negligble. This study provides information on genome-wide chromatin accessibility changes that occur in high density culture in order to study associations with FcgR2b expression.
Project description:The expression of Triggering Receptor Expressed on Myeloid cells (TREM)-1 has been described as a predictive marker for anti-Tumor Necrosis Factor (TNF)-α monoclonal antibody (mAb) therapy responsiveness in patients with inflammatory bowel disease (IBD). Here we investigated expression of TREM-1 specifically in CD14+ monocytes in relation to anti-TNF response. The pretreatment TREM-1 expression levels of CD14+ monocytes of Crohn’s disease (CD) patients were predictive of outcome to anti-TNF mAb therapy, with low TREM-1 expression associated with response to anti-TNF. FACSorting of CD14+ monocytes with different TREM-1 levels showed that differentiation towards regulatory CD206+ M2 type macrophages by anti-TNF was suppressed in CD14+ monocytes with high TREM-1 expression. Activity of the Fcγ-Receptor and autophagy pathway, both necessary for M2 type differentiation and the response to anti-TNF, were decreased in CD14+ monocytes with high expression of TREM-1. We confirmed that the activity of the Fcγ-Receptor pathway was decreased in the CD patients that did not respond to anti-TNF therapy and that it was negatively correlated with TREM-1 expression levels in the CD patient cohort. In conclusion, our results indicate that TREM-1 expression levels in CD14+ monocytes associate with decreased autophagy and FcγR activity resulting in decreased differentiation to M2 type regulatory macrophages upon anti-TNF mAb treatment, which may explain anti-TNF non-response in IBD patients with high expression levels of TREM-1.
Project description:Comparison of circulating monocytes from pre- and postmenopausal females with low or high bone mineral density (BMD). Circulating monocytes are progenitors of osteoclasts, and produce factors important to bone metabolism. Results provide insight into the role of monocytes in osteoporosis. We identify osteoporosis genes by microarray analyses of monocytes in high vs. low hip BMD (bone mineral density) subjects. Microarray analyses of monocytes were performed using Affymetrix 1.0 ST arrays in 73 Caucasian females (age: 47-56) with extremely high (mean ZBMD =1.38, n=42, 16 pre- and 26 postmenopausal subjects) or low hip BMD (mean ZBMD=-1.05, n=31, 15 pre- and 16 postmenopausal subjects). Differential gene expression analysis in high vs. low BMD subjects was conducted in the total cohort as well as pre- and post-menopausal subjects.