⮝ Full datasets listing

PXD046830

PXD046830 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleCC16 drives VLA-2-dependent SPLUNC1 expression.
DescriptionRationale: 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-/- MTECS, 6 of which were validated by mRNA expression in Severe Asthma Research Program (SARP) cohorts. Short Palate Lung and Nasal Epithelial Clone 1 (SPLUNC1) was the most differentially expressed protein (66-fold) and was the focus of this study. Using a combination of MTECs and HNECs, we found that CC16 enhances pulmonary epithelial-driven SPLUNC1 expression via signaling through the receptor complex Very Late Antigen-2 (VLA-2) and that rCC16 given to mice enhances pulmonary SPLUNC1 production and decreases Mycoplasma pneumoniae (Mp) burden. Likewise, rSPLUNC1 results in decreased Mp burden in mice lacking CC16 mice. The VLA-2 integrin binding site within rCC16 is necessary for induction of SPLUNC1 and the reduction in Mp burden. Conclusions: 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.
HostingRepositoryPRIDE
AnnounceDate2023-11-13
AnnouncementXMLSubmission_2023-11-13_09:13:32.249.xml
DigitalObjectIdentifierhttps://dx.doi.org/10.6019/PXD046830
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterPaulLanglais
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListphosphorylated residue; acetylated residue; monohydroxylated residue; iodoacetic acid derivatized residue
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-11-09 15:57:14ID requested
12023-11-13 09:13:32announced
Publication List
10.6019/PXD046830;
Keyword List
submitter keyword: Short Palate Lung and Nasal Epithelial Clone 1,Club Cell Secretory Protein, epithelial-driven host responses
Contact List
JulieLedford
contact affiliationDepartment of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ 85724 Asthma and Airway Disease Research Center, Tucson, AZ 85724
contact emailjledford@arizona.edu
lab head
PaulLanglais
contact affiliationUniversity of Arizona
contact emaillanglais@deptofmed.arizona.edu
dataset submitter
Full Dataset Link List
Dataset FTP location
NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/11/PXD046830
PRIDE project URI
Repository Record List
[ + ]