CC16 Drives Vla-2-Dependent SPLUNC1 Expression

Authors

Natalie Iannuzo
Holly Welfley
Nicholas C Li
Michael D L Johnson
Joselyn Rojas-Quintero
Francesca Polverino
Stefano Guerra
Xingnan Li
Darren A Cusanovich
Paul R Langlais
Julie G Ledford

Publication Date

1-1-2023

Journal

Frontiers in Immunology

DOI

10.3389/fimmu.2023.1277582

PMID

38053993

PMCID

PMC10694244

PubMedCentral® Posted Date

11-20-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Animals, Humans, Mice, Asthma, Integrin alpha2beta1, Lung, Mycoplasma pneumoniae, Signal Transduction, CC16, mycoplasma pneumoniae, SPLUNC1, airway epithelia, mass spectrometry

Abstract

RATIONALE: CC16 (Club Cell Secretory Protein) is a protein produced by club cells and other non-ciliated epithelial cells within the lungs. CC16 has been shown to protect against the development of obstructive lung diseases and attenuate pulmonary pathogen burden. Despite recent advances in understanding CC16 effects in circulation, the biological mechanisms of CC16 in pulmonary epithelial responses have not been elucidated.

OBJECTIVES: We sought to determine if CC16 deficiency impairs epithelial-driven host responses and identify novel receptors expressed within the pulmonary epithelium through which CC16 imparts activity.

METHODS: We utilized mass spectrometry and quantitative proteomics to investigate how CC16 deficiency impacts apically secreted pulmonary epithelial proteins. Mouse tracheal epithelial cells (MTECS), human nasal epithelial cells (HNECs) and mice were studied in naïve conditions and after Mp challenge.

MEASUREMENTS AND MAIN RESULTS: We identified 8 antimicrobial proteins significantly decreased by CC16

CONCLUSION: Our findings demonstrate a novel role for CC16 in epithelial-driven host defense by up-regulating antimicrobials and define a novel epithelial receptor for CC16, VLA-2, through which signaling is necessary for enhanced SPLUNC1 production.

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