Complement C1q essential for aeroallergen sensitization via CSF1R⁺ conventional dendritic cells type 2

Area of Science:

• Immunology
• Allergy and Asthma Research
• Cell Biology

Background:

• Dendritic cells (DCs) are diverse immune cells with specialized functions.
• The conventional type 2 DC subset, CSF1R+cDC2s, is critical for detecting inhaled allergens.

Purpose of the Study:

• To understand how CSF1R+cDC2s recognize inhaled allergens.
• To identify transcriptomic programs and receptor-ligand interactions involved in allergen sensitization by this DC subset.

Main Methods:

• Single-cell RNA sequencing of mouse lung DCs.
• Conventional DC-selective knockout mouse models and allergen sensitization.
• Analysis of human lung transcriptomic data and bronchoalveolar lavage (BAL) samples.

Main Results:

• C1q is selectively enriched in lung CSF1R+cDC2s.
• C1q depletion in DCs reduces allergen sensing and asthma features.
• C1q binds dust mite allergen; its receptor CD91 (LRP1) is essential for CSF1R+cDC2s to induce allergic inflammation.
• C1q is elevated in human BAL post-allergen challenge, with human IGSF21+DCs homologous to mouse CSF1R+cDC2s.

Conclusions:

• CSF1R+cDC2s secrete C1q, a key mediator in allergic lung inflammation.
• The C1q-LRP1 axis is a potential therapeutic target for allergic lung diseases.