Heparan sulfate regulates amphiregulin programming of tissue reparative lung mesenchymal cells during influenza A virus infection in mice

Amphiregulin is an immune cell-derived growth factor that plays critical roles in tissue repair. After influenza A infection, Treg cells in the lung produce amphiregulin, which signals to a specific Col14a1-expressing subpopulation of lung mesenchymal cells (Col14-LMC) to coordinate their repair activities towards the damaged lung epithelium. Heparan sulfate is a subtype of proteoglycan that can be produced by all cells in the body, and has been implicated in altering growth factor signaling in numerous contexts. Amphiregulin has a heparan sulfate-binding domain; we sought to investigate how the inhibition of heparan sulfate on primary Col14-LMC affects their response to amphiregulin at the transcriptional level.