Detection of chimeric alpha-defensin transcripts and peptides in mouse Paneth cells

IntroductionIn mammals, Paneth cells, located in the crypts of the small intestine, produceantimicrobial peptides that serve to keep the intestinal microbiome under control. a-Defensins are the primary antimicrobial peptides produced by these cells.MethodsWe used 148 publicly available bulk RNA-seq...

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Main Authors: Steven Timmermans, Charlotte Wallaeys, Somara De Beul, Natalia Garcia-Gonzales, Claude Libert
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-02-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1543059/full
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author Steven Timmermans
Steven Timmermans
Charlotte Wallaeys
Charlotte Wallaeys
Somara De Beul
Somara De Beul
Natalia Garcia-Gonzales
Natalia Garcia-Gonzales
Claude Libert
Claude Libert
author_facet Steven Timmermans
Steven Timmermans
Charlotte Wallaeys
Charlotte Wallaeys
Somara De Beul
Somara De Beul
Natalia Garcia-Gonzales
Natalia Garcia-Gonzales
Claude Libert
Claude Libert
author_sort Steven Timmermans
collection DOAJ
description IntroductionIn mammals, Paneth cells, located in the crypts of the small intestine, produceantimicrobial peptides that serve to keep the intestinal microbiome under control. a-Defensins are the primary antimicrobial peptides produced by these cells.MethodsWe used 148 publicly available bulk RNA-seq samples on purified PCs, proteomics on enriched purified PC proteins and Defa peptide activity assays to detect all Defa transcrips, including potential chimeric transcrips.ResultsWe identified 28 expressed Defa genes in mice, with up to 85% of Paneth cell RNA reads mapping to these genes. Chimeric mRNAs, involving sequences from two different Defa genes, were detected in most experiments. Despite their low abundance (less than 0.3%), mass spectrometry confirmed the presence of chimeric peptides. Synthetic versions of these peptides demonstrated antibacterial activity against multiple bacterial species.ConclusionWe show the existence of chimeric Defa transcripts and peptides in mice that are biologically active. We propose a possible stochatic mechanism or that the activation of the UPR patway may play a role in their production
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publishDate 2025-02-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Immunology
spelling doaj-art-646c5e06408c4f6cb6f438ceee9ea94e2025-02-06T08:53:32ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-02-011610.3389/fimmu.2025.15430591543059Detection of chimeric alpha-defensin transcripts and peptides in mouse Paneth cellsSteven Timmermans0Steven Timmermans1Charlotte Wallaeys2Charlotte Wallaeys3Somara De Beul4Somara De Beul5Natalia Garcia-Gonzales6Natalia Garcia-Gonzales7Claude Libert8Claude Libert9Center for Inflammation Research, Vlaams Instituut voor Biotechnologie (VIB), Ghent, BelgiumDepartment of Biomedical Molecular Biology, Ghent University, Ghent, BelgiumCenter for Inflammation Research, Vlaams Instituut voor Biotechnologie (VIB), Ghent, BelgiumDepartment of Biomedical Molecular Biology, Ghent University, Ghent, BelgiumCenter for Inflammation Research, Vlaams Instituut voor Biotechnologie (VIB), Ghent, BelgiumDepartment of Biomedical Molecular Biology, Ghent University, Ghent, BelgiumCenter for Inflammation Research, Vlaams Instituut voor Biotechnologie (VIB), Ghent, BelgiumDepartment of Biomedical Molecular Biology, Ghent University, Ghent, BelgiumCenter for Inflammation Research, Vlaams Instituut voor Biotechnologie (VIB), Ghent, BelgiumDepartment of Biomedical Molecular Biology, Ghent University, Ghent, BelgiumIntroductionIn mammals, Paneth cells, located in the crypts of the small intestine, produceantimicrobial peptides that serve to keep the intestinal microbiome under control. a-Defensins are the primary antimicrobial peptides produced by these cells.MethodsWe used 148 publicly available bulk RNA-seq samples on purified PCs, proteomics on enriched purified PC proteins and Defa peptide activity assays to detect all Defa transcrips, including potential chimeric transcrips.ResultsWe identified 28 expressed Defa genes in mice, with up to 85% of Paneth cell RNA reads mapping to these genes. Chimeric mRNAs, involving sequences from two different Defa genes, were detected in most experiments. Despite their low abundance (less than 0.3%), mass spectrometry confirmed the presence of chimeric peptides. Synthetic versions of these peptides demonstrated antibacterial activity against multiple bacterial species.ConclusionWe show the existence of chimeric Defa transcripts and peptides in mice that are biologically active. We propose a possible stochatic mechanism or that the activation of the UPR patway may play a role in their productionhttps://www.frontiersin.org/articles/10.3389/fimmu.2025.1543059/fullalpha-defensinchimeric proteinMus musculusPaneth cellanti-microbial activities
spellingShingle Steven Timmermans
Steven Timmermans
Charlotte Wallaeys
Charlotte Wallaeys
Somara De Beul
Somara De Beul
Natalia Garcia-Gonzales
Natalia Garcia-Gonzales
Claude Libert
Claude Libert
Detection of chimeric alpha-defensin transcripts and peptides in mouse Paneth cells
Frontiers in Immunology
alpha-defensin
chimeric protein
Mus musculus
Paneth cell
anti-microbial activities
title Detection of chimeric alpha-defensin transcripts and peptides in mouse Paneth cells
title_full Detection of chimeric alpha-defensin transcripts and peptides in mouse Paneth cells
title_fullStr Detection of chimeric alpha-defensin transcripts and peptides in mouse Paneth cells
title_full_unstemmed Detection of chimeric alpha-defensin transcripts and peptides in mouse Paneth cells
title_short Detection of chimeric alpha-defensin transcripts and peptides in mouse Paneth cells
title_sort detection of chimeric alpha defensin transcripts and peptides in mouse paneth cells
topic alpha-defensin
chimeric protein
Mus musculus
Paneth cell
anti-microbial activities
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1543059/full
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