ILC-poiesis: Making Tissue ILCs from Blood Jenny Mjösberg, Luca Mazzurana  Immunity  Volume 46, Issue 3, Pages 344-346 (March 2017) DOI: 10.1016/j.immuni.2017.03.002 Copyright © 2017 Elsevier Inc. Terms and Conditions

Figure 1 Model for Differentiation, Tissue Distribution, and Migration of ILCPs during “ILC-poiesis” (Top) Lim et al. describe that fetal liver HSCs can give rise to uni- and multipotent CD117+ ILCPs, which are found in several organs, including the liver. It is possible that ILCPs then enter the circulation and migrate to peripheral organs by yet unknown mechanisms. Speculatively, CD34+ ILCPs are an intermediate in the generation of CD117+ ILCPs from HSCs. However, because CD34+ ILCPs are found in secondary lymphoid tissues (SLTs) but not in peripheral blood, CD34+ ILCPs would have to differentiate to CD117+ ILCPs before entering the circulation. In peripheral organs, ILCPs differentiate to fully mature ILCs, producing the signature cytokines characteristic of each ILC subset. Differentiation to ILC3s most likely involves immature ILC3 intermediates, which express RORγt but do not produce IL-22 or IL-17A. Differentiation to mature ILCs is likely to be influenced by the local immune environment, e.g., inflammation, ensuring that the appropriate ILC populations are timely mobilized. (Bottom) CD34+RORγt− HSCs give rise to CD34−CD117+CD45RA+RORγt− ILCPs either directly or with CD34+CD117+CD45RA+RORγtdim ILCPs (Scoville et al., 2016) as an intermediate. Multipotent CD34−CD117+CD45RA+RORγt− ILCPs are likely to generate unipotent ILCPs, which develop into fully mature ILC1s, ILC2s, ILC3s, or NK cells. CD34−CD117+CD45RA+RORγt+ ILCPs could represent an immature ILC3 subset acting as a transition state in the ILC3 differentiation pathway. Immunity 2017 46, 344-346DOI: (10.1016/j.immuni.2017.03.002) Copyright © 2017 Elsevier Inc. Terms and Conditions