XBP1-mediated activation of the STING signalling pathway in macrophages contributes to liver fibrosis progression

•Macrophage STING signalling can be activated by mtDNA cytosolic leakage from macrophages themselves.•Xbp1 depletion suppresses cGAS/STING/NLRP3 activation by restoring BNIP3-mediated mitophagy activation in macrophages.•XBP1 targets and inhibits the transcription of Bnip3 directly in macrophages.•Myeloid-specific Xbp1 deficiency, or STING deficiency, or Nlrp3 depletion protect livers against fibrosis in mice.•Pharmacological inhibition of XBP1 ameliorates liver fibrosis in mice.