Interestingly, macrophages are instructed by pro-inflammatory mediators (CCL2, IL-8, CXCL1, CXCL10, CXCL12) or EV-mediated DAMP released by cholangiocytes owing to the gain of a senescent phenotype (as in PSC) or the persistence of an immature, fetal-like ciliary defective phenotype (as in CHF). Here, CCL2 is linked to congestive heart failure.