Antigen presentation by lung epithelial cells directs CD4⁺ T_RM cell function and regulates barrier immunity

Area of Science:

• Immunology
• Cell Biology
• Respiratory Medicine

Background:

• Barrier tissues host plastic CD4+ T resident memory (Trm) cells.
• The role of barrier epithelium in regulating Trm cell behavior is largely unknown.

Purpose of the Study:

• To investigate if lung epithelial cells regulate CD4+ Trm cell localization, plasticity, and activities.
• To elucidate the mechanisms by which epithelial cells influence Trm cell function in the lung.

Main Methods:

• Utilized in vivo models to ablate lung epithelial MHC-II.
• Analyzed CD4+ Trm cell localization, transcription factor expression, cytokine profiles, and PD-L1 surface expression.

Main Results:

• Lung epithelial cells, including SPClowMHChigh cells, act as antigen-presenting cells.
• Epithelial MHC-II ablation altered CD4+ Trm cell localization and led to dysregulated barrier immunity.
• Epithelial MHC-II is required for PD-L1 expression, which constrains Trm cell phenotypes.

Conclusions:

• Epithelial antigen presentation critically regulates CD4+ Trm cell function in barrier immunity.
• Epithelial-Trm cell interactions are fundamental to maintaining lung barrier immune homeostasis.