Identification of the niche and mobilization mechanism for tissue-protective multipotential bone marrow ILC progenitors

Innate lymphoid cells (ILCs) play crucial roles in maintenance and defense of peripheral tissues but would undergo natural and inflammation-induced attrition over time. A potential solution to counteract the peripheral ILC attrition would be regulated mobilization of bone marrow (BM) ILC progenitors. The major multipotential ILC progenitors (ILCPs) are divided into two subsets in distinct niches of the BM. Sinusoid ILCPs emigrate from the BM to circulate the peripheral blood. In contrast, parenchyma ILCPs are more likely in cell cycling and less likely to emigrate BM. The mobilization of BM ILCPs is internally and externally controlled by the coordinated expression of the BM retention receptors (Itg-α4 and CXCR4) and the emigration receptors sphingosine-1-phosphate (S1P) receptors. The expression of the BM retention and emigration receptors is developmentally regulated in the steady state and by the inflammasome-derived IL-18. Upon infusion, sinusoid ILCPs can effectively restore peripheral ILC insufficiency and tissue integrity during inflammatory responses.