In Situ Maturation and Tissue Adaptation of Type 2 Innate Lymphoid Cell Progenitors

We analyzed the full spectrum of lung ILC2s at single-cell transcriptome resolution and identified an immature population of Il18r1+ tissue-associated ILCs, that express Tcf7 and Zbtb16, transcription factors known to act in ILC progenitors, and low levels of Gata3, ST2 and ILC2 effector molecules. We revealed a continuous differentiation trajectory and validated the potential of immature Il18r1+ cells to differentiate into Gata3hi ILC2s. We found that immature ILCs were recruited into the adult lung of parabiotic and shield chimeric mice during helminth infection. Intriguingly, recruited cells generated the entire spectrum of ILC2s in the lung, consistent with their potential role in the renewal of tissue ILC2s. Our work identifies local ILC progenitors and highlights their tissue adaptation and in situ differentiation as a mechanism of ILC maintenance and phenotypic diversification Comprehensive single-cell atlas and transcriptome comparison of ILC populations in the BM (Lin-IL18r1+Icos+), and neonatal (liveLin-CD45+Thy1+IL7r+Nk1.1-ST2+/-) and adult lung (LiveLin-CD45+Thy1+IL7r+Nk1.1-) at steady-state, as well as over the course of helminth infection in wild-type, parabiotic and shield chimeric mice,本研究以单细胞转录组分辨率全面分析了肺部2型固有淋巴样细胞（ILC2s），并鉴定出一群Il18r1阳性的组织驻留未成熟固有淋巴样细胞（ILCs）；该细胞群表达在固有淋巴样细胞祖细胞中发挥功能的转录因子Tcf7与Zbtb16，且低表达Gata3、ST2以及ILC2效应分子。本研究揭示了一条连续的分化轨迹，并验证了未成熟Il18r1阳性细胞向Gata3高表达ILC2s（Gata3hi ILC2s）分化的潜能。研究发现，在蠕虫感染过程中，未成熟固有淋巴样细胞会被招募至联体共生与屏蔽嵌合小鼠的成年肺部。有趣的是，被招募的细胞可在肺部生成所有亚型的ILC2s，这与其在组织驻留ILC2s更新过程中的潜在功能相符。本研究鉴定出了局部固有淋巴样细胞祖细胞，并强调了其组织适应性与原位分化是固有淋巴样细胞维持稳态与表型多样化的机制。本数据集包含稳态下以及野生型、联体共生与屏蔽嵌合小鼠在蠕虫感染进程中的多套单细胞转录组图谱与固有淋巴样细胞群的转录组对比数据，涵盖的细胞群包括骨髓（Bone Marrow, BM）中的Lin⁻IL18r1⁺Icos⁺细胞、新生小鼠肺部的liveLin⁻CD45⁺Thy1⁺IL7r⁺Nk1.1⁻ST2⁺/⁻细胞，以及成年小鼠肺部的LiveLin⁻CD45⁺Thy1⁺IL7r⁺Nk1.1⁻细胞。