Dietary and circadian cues regulate gut barrier integrity by synchronizing epithelial cell-macrophage crosstalk

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Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B187
Abstract ID: 4552

Presenting Author:
Chaitanya Dende , Instructor at Univ. of Texas Southwestern Med. Ctr.

Abstract:

Small intestinal epithelial cells (sIECs) form a critical barrier essential for nutrient absorption and host defense. sIECs undergo continuous renewal to maintain their integrity. Phagocytes, such as macrophages, facilitate the clearance of apoptotic cells that enter subepithelial tissues. However, little is known about how sIEC-phagocyte crosstalk maintains barrier integrity. Our study reveals synchrony between sIEC death and the accumulation of a specific subset of macrophages engaged in engulfing dying cells. Notably, we observed a diurnal rhythmicity in the death of sIECs during homeostasis. A fraction of these dying cells enter the subepithelial space, where Tim4+ CD4+ macrophages rhythmically eliminate them. Our findings demonstrate that Tim4+ CD4+ macrophage maintenance depends on dietary vitamin A via macrophage-intrinsic retinoic acid receptor (RAR) signaling. We show that rhythmic Tim4+ CD4+ macrophage accumulation relies on light cues and the macrophage circadian clock. Impaired macrophage RAR signaling disrupts the clearance of dying sIECs, leading to compromised gut barrier integrity and increased bacterial translocation to distant organs. Our work reveals an intricate relationship between sIECs and phagocytes and identifies a crucial role for Tim4+ CD4+ macrophages in maintaining intestinal barrier integrity. Understanding these dynamics could suggest new strategies for maintaining intestinal barrier function during infection and inflammatory disease.