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Modeling Structural Elements and Functional Responses to Lymphatic-Delivered Cues in a Murine Lymph Node on a Chip.

Published version
Peer-reviewed

Repository DOI


Change log

Authors

Mazzaglia, Corrado 
Munir, Hafsa 
Gerigk, Magda 
Huang, Yan Yan Shery  ORCID logo  https://orcid.org/0000-0003-2619-730X

Abstract

Lymph 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.

Description

Publication status: Published


Funder: WD Armstrong Foundation

Keywords

compartmentalization, immune activation, lymph node, matrix, perfuse

Journal Title

Adv Healthc Mater

Conference Name

Journal ISSN

2192-2640
2192-2659

Volume Title

Publisher

Wiley
Sponsorship
Medical Research Council (MC_UU_12022/5)
European Research Council (758865)