Lung CD4⁺ resident memory T cells remodel epithelial responses to accelerate neutrophil recruitment during pneumonia

Area of Science:

• Immunology
• Respiratory Medicine
• Microbiology

Background:

• Prior pneumococcal exposure establishes lung-resident CD4+ T resident memory (T RM) cells.
• These T RM cells enhance neutrophil recruitment against subsequent, different pneumococcal infections.

Purpose of the Study:

• To investigate the crosstalk between CD4+ T RM cells and lung epithelial cells in protective immunity.
• To elucidate the mechanisms by which prior infection history alters lung epithelial cell responses.

Main Methods:

• CD4+ cell depletion experiments in mice.
• Analysis of gene expression (mRNA) in lung epithelial cells.
• Genome-wide expression analysis of lung tissue.
• In vitro studies using cultured lung epithelial cells treated with IL-17A.

Main Results:

• CD4+ T RM cell depletion reduced CXCL5 and neutrophil accumulation in the lungs.
• Lung epithelial cells from previously infected mice showed increased CXCL5 mRNA.
• IL-17A from CD4+ T RM cells stabilized CXCL5 mRNA in epithelial cells, indicating posttranscriptional regulation.
• ~80% of infection-induced epithelial transcriptome changes were CD4+ cell-dependent.

Conclusions:

• Lung epithelial cells are functionally altered by communication with CD4+ T RM cells following infection.
• Tissue-resident adaptive immune cells modulate epithelial cell function to enhance innate immune responses.
• This T RM cell-epithelial cell crosstalk is crucial for optimized defense in previously exposed lungs and may be a general mechanism in mucosal immunology.