Project description:To determine the influence of primary tumors on pre-metastatic lymph nodes, we have employed whole genome microarray expression profiling as a discovery platform to identify gene signatures of stromal cells from tumor-draining lymph nodes, compared with normal lymph nodes. We subcutaneously inoculated C57BL/6 mice with the 4T1 mammary carcinoma. Two weeks later, tumor-draining lymph nodes were dissociated and stromal cells (CD45-) were sorted. Lymph nodes stromal cells from normal mice without tumor bearing were set as controls.
Project description:B cell-interacting reticular cells (BRC) form transcriptionally and topologically stable immune-interacting microenvironments that direct efficient humoral immunity. While several immune niche factors have been elucidated, the cues sustaining BRC function and topology across activation states remain unclear. Here, we employed single cell RNA-sequencing of human lymph node stromal cells and immune cells to analyse local BRC-immune cell interactions and compare them across SLOs and species from additional datasets. Shared BRC subsets were imprinted by tissue-specific gene signatures, but also expressed functionally convergent niche factors that directed regionalized leukocyte composition. Local BRC-immune cell interactions sustained BRC subset identity via immune cell-provided maturation factors. Bidirectional signalling programs were independent of activation state and mirrored across murine and human tissues. Collectively, our data reveal a conserved set of feedforward BRC-immune cell circuits that sustain topologically-organized, functional niches across inflammatory states, lymphoid organs and species.
Project description:We have previously shown that Tregs infiltrating follicular lymphoma lymph nodes (FLN) are quantitatively and qualitatively different than those infiltrating normal and reactive nodes (NLN, RLN, respectively). To gain insight into how such Treg populations differ, we performed RNA sequence (RNAseq) analyses on flow sorted Tregs from all three sources. We identify several molecules that could contribute to the observed increased suppressive capacity of FLN tregs, including upregulation of CTLA-4, IL-10, and GITR, all confirmed by protein expression. In addition, we identify, and confirm functionally, a novel mechanism by which Tregs target to and accumulate within a human tumor microenvironment, through the down regulation of S1PR1, SELL (L-selectin) and CCR7, potentially resulting in greater lymph node retention. In addition we identify and confirm functionally the upregulation of CXCR5, CXCL13 and IL-16 demonstrating the unique ability of the follicular derived Tregs to localize and accumulate within not only the malignant lymph node, but also localize and accumulate within the malignant B cell follicle itself. Such findings offer significant new insights into how FLN Tregs may contribute to the biology of follicular lymphoma and identify several novel therapeutic targets.
Project description:The mesenteric lymph nodes represent the immune response to eggs in schistosome infections,and the analysis of gene expression profiles of the mesenteric lymph nodes from the Vac-Cha (vaccinated with UV attenuated cercariae and challenged with normal cercariae)and Inf-Con (infected with normal cercariae) groups. We used microarrays to detail the global programme of gene expression and identified distinct classes of up-regulated and down-regulated genes.
Project description:This study investigates the gene expression profiles of mesenchymal stromal cells derived from lymph nodes of patients with follicular lymphoma. Using microarray analysis, we identified differentially expressed genes involved in tumor progression and stromal cell differentiation.
Project description:The mesenteric lymph nodes represent the immune response to eggs in schistosome infections,and the analysis of gene expression profiles of the mesenteric lymph nodes from the Vac-Cha (vaccinated with UV attenuated cercariae and challenged with normal cercariae)and Inf-Con (infected with normal cercariae) groups. We used microarrays to detail the global programme of gene expression and identified distinct classes of up-regulated and down-regulated genes. The mesenteric lymph nodes surrounding the cecum from the Vac-Cha and Inf-Con groups were collected at week 8 post challenge and used to analyze the gene profile with Affymetrix microarrays. We sought to obtain the different genes expression profiles between the Vac-Cha group and Inf-Con group.The Vac-Cha group is three pigs vaccinated with UV attenuated Schistosoma japonicum cercariae and challenged with normal Schistosoma japonicum cercariae, and the Inf-Con group is three pigs infected with normal cercariae. Samples pooled per group. A list of differentially-regulated genes can be found in the supplementary file below.
Project description:Lymph node stromal cells (LNSCs) are an important lymphoid tissue cellular type that regulates the immune response and maintain peripheral tolerance. In rheumatoid arthritis, break of tolerance and formation of autoantibodies occurs years before arthritis. Studies in mice have shown lymph nodes activation before the onset of arthritis. We hypothesize that malfunctioning of LNSCs leads to a microenvironment where immune responses are not properly controlled leading to activation of (autoreactive) lymphocytes and the production of autoantibodies. Here we studied human LNSCs and search for differentially expressed genes between RA at risk or RA versus healthy using RNA sequencing in order to identify new therapeutic targets.