TY - JOUR TI - Intestinal goblet cells sample and deliver lumenal antigens by regulated endocytic uptake and transcytosis AU - Gustafsson, Jenny K AU - Davis, Jazmyne E AU - Rappai, Tracy AU - McDonald, Keely G AU - Kulkarni, Devesha H AU - Knoop, Kathryn A AU - Hogan, Simon P AU - Fitzpatrick, James AJ AU - Lencer, Wayne I AU - Newberry, Rodney D A2 - Ten Hagen, Kelly G A2 - Malhotra, Vivek VL - 10 PY - 2021 DA - 2021/10/22 SP - e67292 C1 - eLife 2021;10:e67292 DO - 10.7554/eLife.67292 UR - https://doi.org/10.7554/eLife.67292 AB - Intestinal goblet cells maintain the protective epithelial barrier through mucus secretion and yet sample lumenal substances for immune processing through formation of goblet cell associated antigen passages (GAPs). The cellular biology of GAPs and how these divergent processes are balanced and regulated by goblet cells remains unknown. Using high-resolution light and electron microscopy, we found that in mice, GAPs were formed by an acetylcholine (ACh)-dependent endocytic event remarkable for delivery of fluid-phase cargo retrograde into the trans-golgi network and across the cell by transcytosis – in addition to the expected transport of fluid-phase cargo by endosomes to multi-vesicular bodies and lysosomes. While ACh also induced goblet cells to secrete mucins, ACh-induced GAP formation and mucin secretion were functionally independent and mediated by different receptors and signaling pathways, enabling goblet cells to differentially regulate these processes to accommodate the dynamically changing demands of the mucosal environment for barrier maintenance and sampling of lumenal substances. KW - intestine KW - goblet cells KW - antigen sampling JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -