# Atypical pericapillary Ly6G⁺Nur77⁺ macrophages initiate type-2 immune responses to allergens in the mouse lung

## TL;DR

A specific type of lung macrophage helps start allergic reactions by detecting allergens and guiding immune cells to fight them.

## Contribution

The study identifies a novel macrophage population that initiates Th2 immune responses to allergens in the mouse lung.

## Key findings

- Ly6G+Nur77+ macrophages capture allergens and initiate Th2 responses via PAR2 sensing of Der p 1.
- These macrophages regulate dendritic cell migration through cysteinyl leukotriene production.
- Inhibiting CysLT biosynthesis reduces allergic responses, suggesting therapeutic potential.

## Abstract

The mechanisms of airway allergen sensing and type 2 immune response initiation remain poorly understood. Using a mouse house dust mite (HDM)-induced allergic airway model, we identify a population of lung macrophages located close to alveolar capillaries that express Ly6G and the nuclear receptor Nr4a1/Nur77. These atypical Ly6G+Nur77+ macrophages preferentially capture airway-delivered allergens and play an important role in initiating HDM-driven T helper type 2 (Th2) responses. They sense the major HDM allergen, the cysteine protease Der p 1, via protease-activated receptor 2 (PAR2), and their activation and accumulation require both PAR2 and Nr4a1/Nur77. These Ly6G+Nur77+ macrophages regulate the migration of conventional migratory dendritic cells (mDCs) to draining mediastinal lymph nodes (mLNs) through cysteinyl leukotriene (CysLT) production, which enhances mDC migration toward CCL21 for T cell priming. Inhibiting CysLT biosynthesis reduces mDC migration and dampens Th2 allergic responses, highlighting possible therapeutic avenues in type 2 immunity.

The cellular mechanisms to initiate allergic responses involve various immune cells in the lungs. Here the authors identify a Ly6G+Nur77+ macrophage population involved in initiation of HDM-driven Th2 responses that detect Derp1 allergen through PAR2 and modulate migration of conventional DC to draining lymph nodes via cysteinyl leukotriene production.