The receptor BLT1 is essential on neutrophils in a mouse model of mucous membrane pemphigoid

Title (eng)
The receptor BLT1 is essential on neutrophils in a mouse model of mucous membrane pemphigoid
Author
Tabea Bremer
Author
Sripriya Murthy
Author
Sabrina Patzelt
Author
Paul Schilf
Author
Mareike Neumann
Author
Sina Gonther
Author
Jasper Pruessmann
Author
Wiebke Pruessmann
Author
Enno Schmidt
Author
Thomas Rülicke
Author
Christian D. Sadik
Abstract (eng)
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.
Type (eng)
journal article
Language
[eng]
Persistent identifier
https://phaidra.vetmeduni.ac.at/o:4999
DOI
10.1172/jci.insight.173914
Is in series
Title (eng)
JCI Insight
Volume
10
Issue
20
ISSN
2379-3708
Issued
2025
Number of pages
14
Publication
American Society for Clinical Investigation
Version type (eng)
version of record (published version)
Date issued
2025
Access rights (eng)
open access
License
CC BY 4.0 International
Rights statement (eng)
© 2025, Bremer et al