Date: June 04, 2019. 12:00
Title: Immune Memory Storage in Barrier Tissues
Affiliation: MIT, Broad, and Ragon Institute, USA
Immunological memory helps hosts adapt to and remember diverse environmental challenges. The importance of this defense strategy is underscored by insufficient or excessive activation of classical adaptive immune memory in mammalian barrier tissues. Whether and how non- immune cells contribute to memory responses in tissues remains unclear. Here, we hypothesized that cytokines may also act directly on, and be remembered by, the tissue parenchyma. Specifically, we utilized single-cell RNA-sequencing to identify that allergic inflammatory cytokines can act on epithelial stem cells to influence their state and differentiation trajectory towards mature functional epithelial cell subsets. Our data provide the first-in-human evidence for immune effector cytokines acting to rewire tissue stem cells and indicate that allergic inflammatory barrier dysfunction stems from intrinsically altered epigenetic “memories” in epithelial stem cells. This adds to the growing appreciation that diverse hematopoietic and parenchymal cell types can remember inflammation, and indicates that it is not so much a question of delineating if a cell type beyond an adaptive immune cell can remember an immune event, but rather what and how they remember. I will discuss how understanding circuits of immune memories in barrier tissues can help provide a unified view of memory to environmental exposures (e.g. allergens, antigens, noxious agents, pathogens and microbial communities, etc.) in promoting tissue adaptation.