Highlights d A single-cell atlas of BM ILCs and lung ILCs of healthy, infected, and parabiotic mice d Identification of tissue-associated ILC progenitors in neonatal and adult lung d Cells recruited from BM generate the entire spectrum of ILC2s in infected lungs d Local cues imprint the phenotypes of ILC2s differentiating in the adult lung

Type 2 innate lymphoid cells (ILC2s) are largely tissue-resident cytokine-secreting effector cells associated with allergic inflammation and protective immunity against helminths. Mechanisms that regulate the population dynamics of ILC2s in tissues are poorly understood. In this issue, Symowski C. and Voehringer D. show that Th2 cell-derived IL-4/IL-13 enhance the proliferation and accumulation of ILC2s in the lung of mice infected with the helminth Nippostrongylus brasiliensis. By generating mixed bone marrow chimeras, the authors could demonstrate that this effect requires ILC2-intrinsic expression of STAT6. STAT6-deficient ILC2s showed lower expression of MHC class II molecules on the cell surface suggesting that ILC2s may communicate directly with Th2 cells and receive an antigen-dependent positive feedback signal that leads to ILC2 accumulation in the lung.

Group 2 innate lymphoid cells (ILC2s) possess indispensable roles during type 2–mediated inflammatory diseases. Although their physiological and detrimental immune functions seem to depend on the anatomical compartment they reside, their tissue tropism and the molecular and immunological processes regulating the self-renewal of the local pool of ILC2s in the context of inflammation or infection are incompletely understood. Here, we analyzed the role of the CC-chemokine receptor CCR8 for the biological functions of ILC2s. In vitro and in vivo experiments indicated that CCR8 is in comparison to the related molecule CCR4 less important for migration of these cells. However, we found that activated mouse and human ILC2s produce the CCR8 ligand CCL1 and are a major source of CCL1 in vivo. CCL1 signaling to ILC2s regulates their proliferation and supports their capacity to protect against helminthic infections. In summary, we identify a novel chemokine receptor–dependent mechanism by which ILC2s are regulated during type 2 responses.