phaidra.vetmeduni.ac.at o:4999 DOI 10.1172/jci.insight.173914 The receptor BLT1 is essential on neutrophils in a mouse model of mucous membrane pemphigoid Mucous membrane pemphigoid (MMP) is a mucocutaneous autoimmune blistering disease affecting diverse mucous membranes and the skin with inflammatory blisters and erosions. The pathogenesis of MMP is only poorly understood, but inflammation in MMP is triggered by specific binding of autoantibodies directed to different proteins of the dermal-epidermal/-epithelial junction, subsequently leading to the influx of inflammatory cells, particularly neutrophils, into the dermis. Using the anti-laminin 332 antibody transfer model of MMP, we addressed the molecular mechanisms of neutrophil infiltration and its significance for the eruption of mucocutaneous lesions. Mice deficient in 5-lipoxygenase (Alox5–/–) or in the leukotriene B4 (LTB4) receptor BLT1 (Ltb4r1–/–) were resistant to skin inflammation and exhibited substantially fewer mucosal lesions, with deficiency in either gene compromising the recruitment of neutrophils to the lesion. Furthermore, neutrophil-specific genetic deficiency in Ltb4r1 similarly protected from MMP. Hence, BLT1 was required on neutrophils, and neutrophil recruitment was indispensable for the eruption of lesions in MMP. In line with these findings, the BLT1 inhibitor CP-105,606 ameliorated MMP dose-dependently. Collectively, our results highlight neutrophils and LTB4/BLT1 as key drivers of inflammation in MMP and as promising therapeutic targets. eng 2026-03-13T10:00:55.492Z LOMv1.0 Author BEGIN:VCARD VERSION:3.0 N:Bremer;Tabea; FN:Tabea Bremer END:VCARD BEGIN:VCARD VERSION:3.0 N:Murthy;Sripriya; FN:Sripriya Murthy END:VCARD BEGIN:VCARD VERSION:3.0 N:Patzelt;Sabrina; FN:Sabrina Patzelt X-ORCID:https://orcid.org/0000-0002-1172-3015 END:VCARD BEGIN:VCARD VERSION:3.0 N:Schilf;Paul; FN:Paul Schilf END:VCARD BEGIN:VCARD VERSION:3.0 N:Neumann;Mareike; FN:Mareike Neumann END:VCARD BEGIN:VCARD VERSION:3.0 N:Gonther;Sina; FN:Sina Gonther END:VCARD BEGIN:VCARD VERSION:3.0 N:Pruessmann;Jasper; FN:Jasper Pruessmann END:VCARD BEGIN:VCARD VERSION:3.0 N:Pruessmann;Wiebke; FN:Wiebke Pruessmann END:VCARD BEGIN:VCARD VERSION:3.0 N:Schmidt;Enno; FN:Enno Schmidt END:VCARD BEGIN:VCARD VERSION:3.0 N:Rülicke;Thomas; FN:Thomas Rülicke X-ORCID:https://orcid.org/0000-0002-2121-9496 END:VCARD BEGIN:VCARD VERSION:3.0 N:Sadik;Christian D.; FN:Christian D. Sadik X-ORCID:https://orcid.org/0000-0001-6701-048X END:VCARD https://w3id.org/kim/hcrt/scheme https://w3id.org/kim/hcrt/text Textdokument Text LOMv1.0 yes https://creativecommons.org/licenses/by/4.0 application/pdf 23248649 https://phaidra.vetmeduni.ac.at/o:4999 https://phaidra.vetmeduni.ac.at/api/object/o:4999/thumbnail LOMv1.0 discipline