Affiliation:
1. MRC Cancer Unit University of Cambridge Cambridge CB2 0XZ UK
2. The Nanoscience Centre University of Cambridge Cambridge CB3 0FF UK
3. Helmholtz Institute for Translational Oncology Mainz (HI‐TRON Mainz) 55131 Mainz Germany
4. Division of Dermal Oncoimmunology German Cancer Research Centre (DKFZ) 69120 Heidelberg Germany
5. Department of Engineering University of Cambridge Cambridge CB2 1PZ UK
6. Translational Medical Sciences School of Medicine University of Nottingham Biodiscovery Institute Nottingham NG7 2RD UK
Abstract
AbstractLymph nodes (LNs) are organs of the immune system, critical for maintenance of homeostasis and initiation of immune responses, yet there are few models that accurately recapitulate LN functions in vitro. To tackle this issue, an engineered murine LN (eLN) has been developed, replicating key cellular components of the mouse LN; incorporating primary murine lymphocytes, fibroblastic reticular cells, and lymphatic endothelial cells. T and B cell compartments are incorporated within the eLN that mimic LN cortex and paracortex architectures. When challenged, the eLN elicits both robust inflammatory responses and antigen‐specific immune activation, showing that the system can differentiate between non specific and antigen‐specific stimulation and can be monitored in real time. Beyond immune responses, this model also enables interrogation of changes in stromal cells, thus permitting investigations of all LN cellular components in homeostasis and different disease settings, such as cancer. Here, how LN behavior can be influenced by murine melanoma‐derived factors is presented. In conclusion, the eLN model presents a promising platform for in vitro study of LN biology that will enhance understanding of stromal and immune responses in the murine LN, and in doing so will enable development of novel therapeutic strategies to improve LN responses in disease.
Funder
Medical Research Council
H2020 European Research Council
Cited by
2 articles.
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