Early human lung immune cell development and its role in epithelial cell fate

Abstract

During human development, lungs develop their roles of gas exchange and barrier function. Recent single cell studies have focused on epithelial and mesenchymal cell types, but much less is known about the developing lung immune cells, although the airways are a major site of mucosal immunity after birth. An open question is whether tissue-resident immune cells play a role in shaping the tissue as it develops in utero. In order to address this, we profiled lung immune cells using scRNAseq, smFISH and immunohistochemistry. At the embryonic stage, we observed an early wave of innate immune cells, including ILCs, NK, myeloid cells and lineage progenitors. By the canalicular stage, we detected naive T lymphocytes high in cytotoxicity genes, and mature B lymphocytes, including B1 cells. Our analysis suggests that fetal lungs provide a niche for full B cell maturation. Given the abundance of immune cells, we investigated their possible effect on epithelial maturation and found that IL-1β drives epithelial progenitor exit from self-renewal and differentiation to basal cells in vitro. In vivo, IL-1β-producing myeloid cells were found adjacent to epithelial tips, suggesting that immune cells may direct the developing lung epithelium.

Effective anti-tumor immune responses are orchestrated by immune cell partnership network that functions through tissue homeostatic pathways, not direct cytotoxicity

“…Such tissue-based activation of the immune response is evident from the presence of tissue-resident T memory cells (Trm) 54 which can be explained by the quantum model of T cell activation recently proposed by the last author 55 . Also, the primary function of immune responses has been proposed to be participating in homeostasis of their target cells [56][57][58][59][60][61] . This homeostatic function can explain the observations on inability of auto-reactive T cells to induce autoimmune pancreatitis following adoptive transfer of OVA-specific T cells that recognized and became activated by OVA-expressing pancreas 62 .…”