# LAIR1 prevents excess inflammatory tissue damage in Staphylococcus aureus skin infection and cutaneous T cell lymphoma

## TL;DR

LAIR1 prevents excessive inflammation and tissue damage in skin infections and lymphoma by regulating immune responses.

## Contribution

This study reveals that LAIR1 signaling limits inflammatory tissue damage in S. aureus infections and CTCL.

## Key findings

- Lair1-KO mice showed increased abscesses and dermonecrosis in S. aureus skin infection.
- Loss of LAIR1 led to elevated proinflammatory cytokines, chemokines, and collagen/ECM proteins.
- CTCL lesions showed similar inflammatory and collagen remodeling patterns as Lair1-KO mice.

## Abstract

Patients with cutaneous T cell lymphoma (CTCL) experience high morbidity and mortality due to S. aureus skin infections and sepsis, but the underlying mechanisms remain unclear. We have previously identified high levels of LAIR2, a decoy protein for the inhibitory receptor LAIR1, in advanced CTCL. Mice lack a LAIR2 homolog, so we used Lair1-KO mice to model LAIR2 overexpression. In a model of S. aureus skin infection, Lair1-KO mice had significantly larger abscesses and areas of dermonecrosis compared with WT despite similar bacterial burdens. Lair1 KO exhibited a pattern of increased inflammatory responses in infection and sterile immune stimulation, with increased production of proinflammatory cytokines and myeloid chemokines, neutrophil ROS, and collagen/extracellular matrix (ECM) pathway proteins, including collagens and complement factors. These findings support the notion that loss of LAIR1 signaling causes an excessive inflammatory response that exacerbates tissue damage and does not improve infection control. Underscoring the clinical relevance of our findings, CTCL skin lesions exhibited similarly increased expression in cytokine and collagen/ECM remodeling pathways, suggesting that high levels of LAIR2 promote excessive inflammatory tissue damage and compromise host defense against S. aureus infection. LAIR signaling represents a promising target for therapeutic development in CTCL and other inflammatory diseases.

We demonstrate that loss of LAIR1 results in inflammatory tissue damage and immune defects that leads to S. aureus susceptibility observed in Cutaneous T-cell Lymphoma.