Innate lymphoid cells as the next frontier in cellular therapies

Innate lymphoid cells (ILCs) are a family of immune cells, which are able to swiftly respond to cytokines, stress signals, nutrients and other environmental triggers, allowing them to serve as potent mediators of inflammation, and highlighting their potential role in therapeutics. In humans, ILCs are rare cells and exhibit tissue residency, an aspect of their biology that hinders thorough studies of their differentiation and of their complex inflammatory mechanisms in disease, slowing down gain of essential knowledge for clinical use. To bypass these limitations, Daniela C. Hernández from the Innate Immunity group at the DRFZ, led by Prof. Chiara Romagnani, describes an in vitro platform which utilizes CD34⁺ hematopoietic progenitor cells to generate human ILCs – similar to the T cell generation systems of the 90s which propelled T cell biology studies forward. These generated ILCs recapitulate the identities of their ex vivo counterparts in phenotype and functionality, as validated through complex methods such as protein phenotyping with flow cytometry, and transcriptome analysis through both bulk and single cell RNA sequencing. A thorough description of the cells and flexibility of the system enables not only the study of progenitor pathways and lineage making decisions, but also allows for sufficient numbers to target in functionality analyses, to pave the road for preclinical human ILC adoptive transfer studies.