GM-CSF-dependent CD301b+ lung dendritic cells confer tolerance to inhaled allergens

Area of Science:

• Immunology
• Cell Biology
• Respiratory Medicine

Background:

• Allergic asthma severity depends on the balance between T regulatory (Treg) and T helper (Th)2 cells.
• The role of specific dendritic cell subsets in directing Treg and Th2 cell differentiation remains unclear.

Purpose of the Study:

• To identify conventional dendritic cell (cDC) subsets that regulate Treg and Th2 cell differentiation.
• To investigate the function of CD301b+ type 2 cDCs (cDC2s) in allergic sensitization and lung homeostasis.

Main Methods:

• Single-cell RNA sequencing was used to analyze cDC subsets.
• Adoptive transfer experiments in mice were performed to assess T cell differentiation and immune tolerance.
• The role of GM-CSF in cDC development and function was evaluated.

Main Results:

• A subset of lung-resident cDC2s expressing high CD301b demonstrated potent Treg-inducing activity ex vivo.
• During allergic sensitization, CD301b+ cDC2s transitioned to CD200+ cDC2s, promoting Th2 differentiation.
• GM-CSF augmented the development and maintenance of Treg-inducing CD301b+ cDC2s in vivo.
• Adoptive transfer of lung-derived CD301b+ cDC2s conferred tolerance to inhaled allergens.

Conclusions:

• Lung-resident CD301b+ cDC2s play a critical role in inducing Treg cells and promoting immunological tolerance.
• GM-CSF supports lung homeostasis by increasing the number of Treg-inducing CD301b+ cDC2s.