Mebius Lab

The adaptive immune system is initiated in secondary lymphoid organs such as lymph nodes. We are developing 3D human lymph node organotypic cultures, in order to include the immune system in multi-organ on chip devices. For the formation of lymph nodes, stromal cells are crucially involved through interaction with hematopoietic lymphoid tissue inducer cells (LTi cells). Once these structures are formed, lymph nodes stromal cells microenvironments within lymph nodes, allowing efficient B-T cell interactions. In addition, lymph node stromal cells are modulating the ongoing immune response. In our research on developing 3D lymph node cultures, we are therefore including these stromal cells, as well as hematopoietic cells, allowing the study of their effects on the adaptive immune response. In addition, by connecting lymph nodes to tissue in a multi-organ chip, we can study the effects of tissue drainage on lymph node functioning in homeostasis and pathological conditions.

Team leader

Reina E. Mebius

Professor, Molecular Cell Biology, with focus on development immune system

Reina Mebius is a principal investigator at the department of Molecular Cell Biology and Immunology at the Amsterdam UMC, location VUmc. Her work is focused on the micro-environmental control of immune reactions, ranging from lymph node development to immune reactions within cancer and autoimmune patients.

From the studies of lymph node development, her team discovered how the interaction between stromal cells and immune cells is crucial for the development of lymph nodes. This initiated studies into the role of the microenvironment on immune cells and vice versa. In one research line they showed how diet, vitamin A as well as the microbiome all affect the state of immune tolerance within the intestine. In related research, her team showed that stromal cells within lymph nodes can present self-antigens thereby converting naïve T cells to become regulatory T cells, which control adaptive immune responses as well as maintaining these regulatory T cells. Her lab is currently using this knowledge to construct human lymph nodes in 3D culture systems.

Team members

Lotte (C.M.) de Winde
Postdoctoral research fellow

Andrew Morrison
PhD student

Daphne Panocha
PhD student

Publications

• Expanded Polyglutamine-containing N-terminal Huntingtin Fragments Are Entirely Degraded by Mammalian Proteasomes
  Abstract Huntington disease is a neurodegenerative disorder caused by an…   »
• Development of follicular dendritic cells in lymph nodes depends on retinoic acid-mediated signaling
  Specialized stromal cells occupy and help define B- and T-cell…   »
• Lymph node stromal cells: subsets and functions in health and disease
  Lymph nodes (LNs) aid the interaction between lymphocytes and antigen-presenting…   »
• Stromal cells and immune cells involved in formation of lymph nodes and their niches
  Secondary lymphoid organs are critical for efficient interaction between innate antigen presenting cells and…   »
• Lymph Node Stromal Cells Generate Antigen-Specific Regulatory T Cells and Control Autoreactive T and B Cell Responses
  Within lymph nodes (LNs), T follicular helper (TFH) cells help…   »
• Nestin-Expressing Precursors Give Rise to Both Endothelial as well as Nonendothelial Lymph Node Stromal Cells
  During embryogenesis, lymph nodes form through intimate interaction between lymphoid…   »

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Funding

• ARCAID consortium (EU-Horizon 2020 CoFund)
• NWA-ORC consortium LymphChip (NWO)
• Cancer Center Amsterdam Research Grant (CCA2019-9-57): Interfering with antigen-presenting stromal cells in lymph nodes to block regulatory T cell conversion and boost antitumor immunity
• Institute for Chemical Immunology (NWO): Mechanisms of self-antigen expression in tolerance inducing lymph node stromal cells
• Cancer Center Amsterdam Research Grant (CCA2020-9-73) to Lotte de Winde for project “Development of an in vitro human B-cell lymphoma model to study cancer dissemination”.