Neuro-immune regulation of type 2 innate lymphoid cells (ILC2s) in bladder cancer

Innate lymphoid cells have emerged as a potent innate immune cell population with key roles in homeostasis, as well as in forming first line of defense against infections. Increasing evidences also highlight their involvement in different pathologies such as inflammatory diseases and cancers. Extensive work is being performed by us and others to unravel ILC biology and their underlying mechanisms of actions, both in physiology and in diseases. In this work, we were able to decipher the complex transcriptomic and epigenetic regulation of human peripheral ILCs. We exposed and identified a high inter-subsets complexity, with each core ILC subset (i.e., ILC1s, ILC2s, ILCPs) further divided in subclusters, showing a high level of heterogeneity and providing a resource database for future studies in patients. In addition, we uncovered the underlying mechanisms leading to ILC2 pro-tumoral phenotype in bladder cancer, highlighting for the first time the role of a neurotrophic factor, NGF, regulating ILC2 functions in the context of tumor immunity. </p

ILC2s: new actors in tumor immunity

Innate lymphoid cells (ILCs) represent the most recently identified family of innate lymphocytes that act as first responders, maintaining tissue homeostasis and protecting epithelial barriers. In the last few years, group 2 ILCs (ILC2s) have emerged as key regulators in several immunological processes such as asthma and allergy. Whilst ILC2s are currently being evaluated as novel targets for immunotherapy in these diseases, their involvement in tumor immunity has only recently begun to be deciphered. Here, we provide a comprehensive overview of the pleiotropic roles of ILC2s in different tumor settings. Furthermore, we discuss how different therapeutic approaches targeting ILC2s could improve the efficacy of current tumor immunotherapies

Healthy and patient type 2 innate lymphoid cells are differently affected by in vitro culture conditions

Type 2 innate lymphoid cells (ILC2s) have emerged as key players in the development of type 2 driven diseases such as allergy and asthma. Due to their low number in the circulation, in vitro expansion is needed to unravel their mechanisms of action

Dynamic single-cell regulomes characterize human peripheral blood innate lymphoid cell subpopulations

Summary: Innate lymphoid cells (ILCs) are plastic immune cells divided into 3 main subsets, characterized by distinct phenotypic and functional profiles. Using single cell approaches, heightened heterogeneity of mouse ILCs has been appreciated, imprinted by tissue signals that shape their transcriptome and epigenome. Intra-subset diversity has also been observed in human ILCs. However, combined transcriptomic and epigenetic analyses of single ILCs in humans are lacking.Here, we show high transcriptional and epigenetic heterogeneity among human circulating ILCs in healthy individuals. We describe phenotypically distinct subclusters and diverse chromatin accessibility within main ILC populations, compatible with differentially poised states. We validate the use of this healthy donor-based analysis as resource dataset to help inferring ILC changes occurring in disease conditions. Overall, our work provides insights in the complex human ILC biology. We anticipate it to facilitate hypothesis-driven studies in patients, without the need to perform single cell OMICs using precious patients’ material