34: Hematopoietic Stem/Progenitor Cell Dependent Participation of Innate Lymphoid Cells in Low-Intensity Sterile Inflammation

Innate lymphoid cells (ILCs) are increasingly acknowledged as important mediators of immune homeostasis and pathology. They act as early orchestrators of immunity and as such they make up interesting therapeutic targets for several diseases and possibly a means to peripheral tolerance. Taking advantage of an animal model of sterile peritonitis, induced by intraperitoneal injection of zymosan, a fungal derived TLR-2 ligand we studied the progenitor–successor relationship between the hematopoietic stem/progenitor cells (HSPC) and ILCs at the site of sterile inflammation. Our results demonstrate that the strength of the inflammatory signal affects the capacity of BM-derived HSPCs to migrate and give rise in situ to ILCs. Both low- and high-dose of zymosan injections triggered the appearance of mature ILCs in the peritoneal cavity. Only in low-dose injected mice, the recovered ILCs seemed to be dependent on an in situ differentiation of BM-derived HSPCs and/or ILC2 precursors (ILC2P) wherein high-dose, the stronger inflammatory environment seemed to be able to induce the emergence of ILCs independently of BM-derived HSPCs. To further elucidate the importance of the inflammatory environment per se for the attraction of mature ILCs, an anti- inflammatory drug was used. Treatment of mice with alpha-1 anti-trypsin (AAT) 15 min after injection of either low- or high- dose of zymosan, led to the blockade of the migration of HSPCs into the peritoneal cavity resulting in a loss of even mature ILCs in mice injected with the low-dose of zymosan. Contrary, in mice injected with high-dose, progenitor cells of type 2 of ILCs could be still recovered, but not mature ILC2 cells. We suggest that the relationship between HSPCs and ILCs seem to be affected by the strength of the inflammatory stimuli and that the use of anti-inflammatory molecules like A1 antitrypsin may attenuate the inflammation and to some extent prevent the migration of HSCPs to the site of inflammation and the emergence of mature ILCs.