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


ABSTRACT: Previous pneumococcal experience establishes lung-resident IL-17A-producing CD4+ memory TRM cells that accelerate neutrophil recruitment against heterotypic pneumococci. Herein, we unravel a novel crosstalk between CD4+ TRM cells and lung epithelial cells underlying this protective immunity. Depletion of CD4+ cells in pneumococcus-experienced mice diminished CXCL5 (but not CXCL1 or CXCL2) and downstream neutrophil accumulation in the lungs. Epithelial cells from experienced lungs exhibited elevated mRNA for CXCL5 but not other epithelial products such as GM-CSF or CCL20, suggesting a skewing by CD4+ TRM cells. Genome-wide expression analyses revealed a significant remodeling of the epithelial transcriptome of infected lungs due to infection history, ~80% of which was CD4+ cell-dependent. The CD4+ TRM cell product IL-17A stabilized CXCL5 but not GM-CSF or CCL20 mRNA in cultured lung epithelial cells, implicating posttranscriptional regulation as a mechanism for altered epithelial responses. These results suggest that epithelial cells in experienced lungs are effectively different, owing to their communication with TRM cells. Our study highlights the role of tissue-resident adaptive immune cells in fine-tuning epithelial functions to hasten innate immune responses and optimize defense in experienced lungs, a concept that may apply broadly to mucosal immunology.

SUBMITTER: Shenoy AT 

PROVIDER: S-EPMC7044037 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Lung CD4<sup>+</sup> resident memory T cells remodel epithelial responses to accelerate neutrophil recruitment during pneumonia.

Shenoy Anukul T AT   Wasserman Gregory A GA   Arafa Emad I EI   Wooten Alicia K AK   Smith Nicole M S NMS   Martin Ian M C IMC   Jones Matthew R MR   Quinton Lee J LJ   Mizgerd Joseph P JP  

Mucosal immunology 20191120 2


Previous pneumococcal experience establishes lung-resident IL-17A-producing CD4<sup>+</sup> memory T<sub>RM</sub> cells that accelerate neutrophil recruitment against heterotypic pneumococci. Herein, we unravel a novel crosstalk between CD4<sup>+</sup> T<sub>RM</sub> cells and lung epithelial cells underlying this protective immunity. Depletion of CD4<sup>+</sup> cells in pneumococcus-experienced mice diminished CXCL5 (but not CXCL1 or CXCL2) and downstream neutrophil accumulation in the lungs.  ...[more]

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