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http://purl.uniprot.org/citations/31539206http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/31539206http://www.w3.org/2000/01/rdf-schema#comment"

Background

Protease-activated receptor-1 (PAR-1) plays a major role in multiple disease processes, including colitis. Understanding the mechanisms coupling PAR-1 to disease pathogenesis is complicated by the fact that PAR-1 is broadly expressed across multiple cell types.

Objective

Determine the specific contributions of PAR-1 expressed by macrophages and colonic enterocytes to infectious colitis.

Methods

Mice carrying a conditional PAR-1 allele were generated and bred to mice expressing Cre recombinase in a myeloid-(PAR-1ΔM ) or enterocyte-specific (PAR-1ΔEPI ) fashion. Citrobacter rodentium colitis pathogenesis was analyzed in mice with global PAR-1 deletion (PAR-1-/- ) and cell type-specific deletions.

Results

Constitutive deletion of PAR-1 had no significant impact on weight loss, crypt hypertrophy, crypt abscess formation, or leukocyte infiltration in Citrobacter colitis. However, colonic shortening was significantly blunted in infected PAR-1-/- mice, and these animals exhibited decreased local levels of IL-1β, IL-22, IL-6, and IL-17A. In contrast, infected PAR-1ΔM mice lost less weight and had fewer crypt abscesses relative to controls. PAR-1ΔM mice had diminished CD3+ T cell infiltration into colonic tissue, but macrophage and CD4+ T cell infiltration were similar to controls. Also contrasting results in global knockouts, PAR-1ΔM mice exhibited lower levels of IL-1β, but not Th17-related cytokines (ie, IL-22, IL-6, IL-17A). Infected PAR-1ΔEPI mice exhibited increased crypt hypertrophy and crypt abscess formation, but local cytokine elaboration was similar to controls.

Conclusions

These studies reveal complex, cell type-specific roles for PAR-1 in modulating the immune response to Citrobacter colitis that are not readily apparent in analyses limited to mice with global PAR-1 deficiency."xsd:string
http://purl.uniprot.org/citations/31539206http://purl.org/dc/terms/identifier"doi:10.1111/jth.14641"xsd:string
http://purl.uniprot.org/citations/31539206http://purl.uniprot.org/core/author"Shafer J."xsd:string
http://purl.uniprot.org/citations/31539206http://purl.uniprot.org/core/author"Antoniak S."xsd:string
http://purl.uniprot.org/citations/31539206http://purl.uniprot.org/core/author"Mackman N."xsd:string
http://purl.uniprot.org/citations/31539206http://purl.uniprot.org/core/author"Flick M.J."xsd:string
http://purl.uniprot.org/citations/31539206http://purl.uniprot.org/core/author"Alenghat T."xsd:string
http://purl.uniprot.org/citations/31539206http://purl.uniprot.org/core/author"Lane A."xsd:string
http://purl.uniprot.org/citations/31539206http://purl.uniprot.org/core/author"Sharma B.K."xsd:string
http://purl.uniprot.org/citations/31539206http://purl.uniprot.org/core/author"McKell M.C."xsd:string
http://purl.uniprot.org/citations/31539206http://purl.uniprot.org/core/author"Steinbrecher K.A."xsd:string
http://purl.uniprot.org/citations/31539206http://purl.uniprot.org/core/author"Palumbo J.S."xsd:string
http://purl.uniprot.org/citations/31539206http://purl.uniprot.org/core/author"Boucher A.A."xsd:string
http://purl.uniprot.org/citations/31539206http://purl.uniprot.org/core/author"Rosenfeldt L."xsd:string
http://purl.uniprot.org/citations/31539206http://purl.uniprot.org/core/author"Whitt J."xsd:string
http://purl.uniprot.org/citations/31539206http://purl.uniprot.org/core/author"Crowther R.R."xsd:string
http://purl.uniprot.org/citations/31539206http://purl.uniprot.org/core/author"Mureb D."xsd:string
http://purl.uniprot.org/citations/31539206http://purl.uniprot.org/core/author"Qualls J."xsd:string
http://purl.uniprot.org/citations/31539206http://purl.uniprot.org/core/date"2020"xsd:gYear
http://purl.uniprot.org/citations/31539206http://purl.uniprot.org/core/name"J Thromb Haemost"xsd:string
http://purl.uniprot.org/citations/31539206http://purl.uniprot.org/core/pages"91-103"xsd:string
http://purl.uniprot.org/citations/31539206http://purl.uniprot.org/core/title"Cell type-specific mechanisms coupling protease-activated receptor-1 to infectious colitis pathogenesis."xsd:string
http://purl.uniprot.org/citations/31539206http://purl.uniprot.org/core/volume"18"xsd:string
http://purl.uniprot.org/citations/31539206http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/31539206
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