Ex vivo model of functioning human lymph node reveals role for innate lymphocytes and stroma in response to vaccine adjuvant (2025, Cell Reports)

Our understanding of how vaccines and other immunotherapies work is limited because we lack good models that accurately mimic the human immune system. Inbred mice, commonly used in research, don't have the same immune diversity as humans, and studying isolated immune cells outside of their normal tissue context loses crucial information about how they interact.
Here is a new model system, based on precision-cut lymph node (LN) slices that maintain tissue structure and function, in which we studied the early inflammatory response to a potent vaccine adjuvant LMQ (LMQ contains liposomes and two immunostimulators: a TLR4 agonist and QS21 saponin).
By combining sequencing, imaging and proteomic analyses, we mapped the signalling pathways triggered by the LMQ adjuvant, and observed how different immune cells communicate, linking the early innate response with subsequent generation of adaptive immunity. The stromal cells (LN matrix) in particular were found to directly respond to the adjuvant, orchestrating the downstream responses of other, migratory, immune cells.
This LN model preserves the individual variation in immune responses between people, allowing to study the complex immune processes previously difficult to observe directly in humans, and offering a promising path towards personalised medicine.