Project description:Because of their central role in inflammatory processes pathological alterations in lymph nodes can affect innate and adaptive immunity. However, interpretation of lymph node pathology in humans is hampered by the lack of a reference under homeostatic conditions and a limited understanding of the molecular processes that occur during inflammatory activation. Using a combination of confocal microscopy, flow cytometry, and single cell and spatial transcriptome analysis, our study provides an in-depth characterization of the immunoanatomy of clinically inflammed and non-inflamed human lymph nodes.
Project description:Because of their central role in inflammatory processes pathological alterations in lymph nodes can affect innate and adaptive immunity. However, interpretation of lymph node pathology in humans is hampered by the lack of a reference under homeostatic conditions and a limited understanding of the molecular processes that occur during inflammatory activation. Using a combination of confocal microscopy, flow cytometry, and single cell and spatial transcriptome analysis, our study provides an in-depth characterization of the immunoanatomy of clinically inflammed and non-inflamed human lymph nodes.
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 spatial transcriptome analysis of murine ingunal and mesenteric lymph nodes to examine co-localization of distinct BRC subsets and immune cells complementing BRC-immune cell interaction analysis. Spatial analysis supported predicted feedforward BRC-immune cell circuits that sustain topologically-organized, functional niches across inflammatory states, lymphoid organs and species.
Project description:The non-leukocytic stromal cells of lymph nodes critically regulate immune responsiveness. However, the effects of different SARS-CoV-2 vaccines on stromal cell biology are unknown. We used single-cell transcriptomics to study early responses of stromal cells in draining lymph nodes after immunizing mice with clinically used COVID-19 vaccines, namely Spikevax®, Comirnaty®, Vaxzevria® and Nuvaxovid™. We found that vaccinations lead to robust transcriptomic changes, including vaccine-selective ones, in the different lymph node stromal cell populations priming the lymph node for the upcoming adaptive immune response.
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: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 B 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 B cells (CD19+) were sorted. Lymph nodes B cells from normal mice without tumor bearing were set as controls.