Crosstalk between ILC2 and their supportive niches, gatekeepers of bone marrow homeostatic functions? – CINIMA

Type 2 innate lymphoid cells (ILC2s) share cytokine and transcription factor expression with Th2 lymphocytes. ILC2s promote tissue repair and immune responses to parasitic infections in mucosal barriers. They regulate Th2 environmental and tissue metabolic homeostasis in numerous tissues like the adipose tissue. ILC2s colonize the peripheral niches from the perinatal period and the molecular mechanisms of their in situ maintenance have not yet been explained. The significant accumulation of donor ILC2s after reconstitution with donor bone marrow (BM) in case of myeloablation proved that central mechanisms are in play within the BM to stimulate lymphoid precursors to produce new ILC2s. Hence, we will identify and characterize the BM stromal cell compartment supporting ILC2 development using confocal microscopy, cytometry and single cell RNA sequencing in normal and ILC2 defective models. We will determine whether ILC2/niche interactions could evolve with age and during obesity driven inflammation. Our data point to a specific role for BM ILC2s in perpetuating a healthy hematopoiesis that we propose to mechanistically address.