Our results indicate (a) that cells on the periphery of the fibroblastic focus display markers of hypoxia that codistribute with IPF MPCs and (b) that hypoxia creates a feed-forward loop that enhances IPF MPC fibrogenicity via augmenting lactate production, release, and signaling via the GPR81 lactate receptor. Here, HCAR1 is linked to idiopathic pulmonary fibrosis.