Boosting Apoptotic Cell Clearance by Colonic Epithelial Cells Attenuates Inflammation In Vivo.

Chang Sup Lee, Kristen K Penberthy, Karen M Wheeler, Ignacio J Juncadella, Peter Vandenabeele, Jeffrey J Lysiak, Kodi S Ravichandran

Immunity 2016 Apr 19

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Few apoptotic corpses are seen even in tissues with high cellular turnover, leading to the notion that the capacity for engulfment in vivo is vast. Whether corpse clearance can be enhanced in vivo for potential benefit is not known. In a colonic inflammation model, we noted that the expression of the phagocytic receptor Bai1 was progressively downmodulated. Consistent with this, BAI1-deficient mice had more pronounced colitis and lower survival, with many uncleared apoptotic corpses and inflammatory cytokines within the colonic epithelium. When we engineered and tested transgenic mice overexpressing BAI1, these had fewer apoptotic cells, reduced inflammation, and attenuated disease. Boosting BAI1-mediated uptake by intestinal epithelial cells (rather than myeloid cells) was important in attenuating inflammation. A signaling-deficient BAI1 transgene could not provide a similar benefit. Collectively, these complementary genetic approaches showed that cell clearance could be boosted in vivo, with potential to regulate tissue inflammation in specific contexts. Copyright © 2016 Elsevier Inc. All rights reserved.

Citation

Chang Sup Lee, Kristen K Penberthy, Karen M Wheeler, Ignacio J Juncadella, Peter Vandenabeele, Jeffrey J Lysiak, Kodi S Ravichandran. Boosting Apoptotic Cell Clearance by Colonic Epithelial Cells Attenuates Inflammation In Vivo. Immunity. 2016 Apr 19;44(4):807-20