Innate lymphoid cells facilitate NK cell development through a lymphotoxinmediated stromal microenvironment

Natural killer (NK) cell development relies on signals provided from the bone marrow (BM) microenvironment. It is thought that lymphotoxin (LT) α₁β₂ expressed by the NK cell lineage interacts with BM stromal cells to promote NK cell development. However, we now report that a small number of RORγ^t+ innate lymphoid cells (ILCs), and not CD3-NK1.1⁺ cells, express LT to drive NK development. Similar to LT^-/- or RORγ^t-/- mice, the mice conditionally lacking LTα₁β₂ on RORγ^t+ ILCs experience a developmental arrest at the immature NK stages, between stages of NK development to the mature NK cell stage. This developmental block results in a functional deficiency in the clearance of NK-sensitive tumor cells. Reconstitution of Thy1⁺ ILCs from BM or purified RORγ^t+ ILCs from lamina propria lymphocytes into LT-deficient RORγ^t+ BM cultures rescues NK cell development. These data highlight a previously undiscovered role of RORγ^t+ ILCs for NK cell development and define LT from ILCs as an essential molecule for the stromal microenvironment supporting NK cell development.