RT Journal Article
SR Electronic
T1 An anti-inflammatory activation sequence governs macrophage transcriptional dynamics during tissue injury
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.09.28.462132
DO 10.1101/2021.09.28.462132
A1 Nicolas Denans
A1 Nhung T. T. Tran
A1 Madeleine E. Swall
A1 Daniel C. Diaz
A1 Jillian Blanck
A1 Tatjana Piotrowski
YR 2021
UL http://biorxiv.org/content/early/2021/09/30/2021.09.28.462132.abstract
AB Macrophages are essential for tissue repair and regeneration. Yet, the molecular programs, as well as the timing of their activation during and after tissue injury are poorly defined. Using a high spatio-temporal resolution single cell analysis of macrophages coupled with live imaging after sensory hair cell death in zebrafish, we find that the same population of macrophages transitions through a sequence of three major anti-inflammatory activation states. Macrophages first show a signature of glucocorticoid activation, then IL10 signaling and finally the induction of oxidative phosphorylation by IL4/Polyamine signaling. Importantly, loss-of-function of glucocorticoid and IL10 signaling shows that each step of the sequence is independently activated. Our results provide the first evidence that macrophages, in addition to a switch from M1 to M2, sequentially and independently transition though three anti-inflammatory pathways in vivo during tissue injury in a regenerating organ.One-Sentence Summary We show that macrophages are sequentially activated by three different anti-inflammatory pathways during tissue injury.Competing Interest StatementThe authors have declared no competing interest.