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dc.contributor.authorSaul-McBeth, Jessica
dc.contributor.authorDillon, John
dc.contributor.authorLee, Aaron
dc.contributor.authorLaunder, Dylan
dc.contributor.authorKratch, Jacqueline M
dc.contributor.authorAbutaha, Eanas
dc.contributor.authorWilliamson, Alexandria A
dc.contributor.authorSchroering, Allen G
dc.contributor.authorMichalski, Grace
dc.contributor.authorBiswas, Priosmita
dc.contributor.authorConti, Samuel R
dc.contributor.authorShetty, Amol C
dc.contributor.authorMcCracken, Carrie
dc.contributor.authorBruno, Vincent M
dc.contributor.authorParsai, E Ishmael
dc.contributor.authorConti, Heather R
dc.date.accessioned2021-07-07T16:32:26Z
dc.date.available2021-07-07T16:32:26Z
dc.date.issued2021-06-17
dc.identifier.urihttp://hdl.handle.net/10713/16140
dc.description.abstractOral mucositis (OM) is a treatment-limiting adverse side effect of radiation and chemotherapy. Approximately 80% of patients undergoing radiotherapy (RT) for head and neck cancers (HNC) develop OM, representing a major unmet medical condition. Our understanding of the immunopathogenesis of OM is limited, due in part to the surprising paucity of information regarding healing mechanisms in the oral mucosa. RNAseq of oral tissue in a murine model that closely mimics human OM, showed elevated expression of IL-17 and related immune pathways in response to head and neck irradiation (HNI). Strikingly, mice lacking the IL-17 receptor (IL-17RA) exhibited markedly more severe OM. Restoration of the oral mucosa was compromised in Il17ra-/- mice and components associated with healing, including matrix metalloproteinase 3, 10 and IL-24 were diminished. IL-17 is typically associated with recruitment of neutrophils to mucosal sites following oral infections. Unexpectedly, in OM the absence of IL-17RA resulted in excessive neutrophil recruitment and immunopathology. Instead, neutrophil activation was IL-1R-driven in Il17ra-/- mice. Blockade of IL-1R and depletion of neutrophils lessened the severity of damage in these mice. Overall, we show IL-17 is protective in OM through multiple mechanisms including restoration of the damaged epithelia and control of the neutrophil response. We also present a clinically relevant murine model of human OM to improve mechanistic understanding and develop rational translational therapeutics.en_US
dc.description.urihttps://doi.org/10.3389/fimmu.2021.687627en_US
dc.language.isoenen_US
dc.publisherFrontiers Media S.A.en_US
dc.relation.ispartofFrontiers in Immunologyen_US
dc.rightsCopyright © 2021 Saul-McBeth, Dillon, Lee, Launder, Kratch, Abutaha, Williamson, Schroering, Michalski, Biswas, Conti, Shetty, McCracken, Bruno, Parsai and Conti.en_US
dc.subjecthealingen_US
dc.subjectinflammationen_US
dc.subjectinterleukin-17en_US
dc.subjectoral mucosaen_US
dc.subjectoral mucositis (OM)en_US
dc.titleTissue Damage in Radiation-Induced Oral Mucositis Is Mitigated by IL-17 Receptor Signalingen_US
dc.typeArticleen_US
dc.identifier.doi10.3389/fimmu.2021.687627
dc.identifier.pmid34220843
dc.source.volume12
dc.source.beginpage687627
dc.source.endpage
dc.source.countrySwitzerland


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