Abstract:
: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.
journal_name
Immunityjournal_title
Immunityauthors
Lee CS,Penberthy KK,Wheeler KM,Juncadella IJ,Vandenabeele P,Lysiak JJ,Ravichandran KSdoi
10.1016/j.immuni.2016.02.005subject
Has Abstractpub_date
2016-04-19 00:00:00pages
807-20issue
4eissn
1074-7613issn
1097-4180pii
S1074-7613(16)30020-6journal_volume
44pub_type
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