Tissue Damage in Radiation-Induced Oral Mucositis Is Mitigated by IL-17 Receptor Signaling
| العنوان: | Tissue Damage in Radiation-Induced Oral Mucositis Is Mitigated by IL-17 Receptor Signaling |
|---|---|
| المؤلفون: | Jessica Saul-McBeth, Heather R. Conti, E. Ishmael Parsai, John Dillon, Alexandria A. Williamson, Dylan Launder, Jacqueline M. Kratch, Allen Schroering, Carrie McCracken, Eanas Abutaha, Samuel Richard Conti, Priosmita Biswas, Aaron Lee, Amol C. Shetty, Grace Michalski, Vincent M. Bruno |
| المصدر: | Frontiers in Immunology, Vol 12 (2021) Frontiers in Immunology |
| بيانات النشر: | Frontiers Media SA, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Side effect, Cell Survival, Immunology, Inflammation, interleukin-17, 03 medical and health sciences, 0302 clinical medicine, Immune system, Tongue, Immunopathology, Mucositis, Animals, Immunology and Allergy, Medicine, Oral mucosa, Radiation Injuries, Receptor, Cell Proliferation, Original Research, Mice, Knockout, Stomatitis, Wound Healing, Receptors, Interleukin-17, oral mucosa, business.industry, Receptors, Interleukin-1, oral mucositis (OM), RC581-607, healing, medicine.disease, Disease Models, Animal, 030104 developmental biology, medicine.anatomical_structure, Neutrophil Infiltration, inflammation, 030220 oncology & carcinogenesis, Cancer research, Interleukin 17, Immunologic diseases. Allergy, medicine.symptom, Transcriptome, business, Interleukin-1, Signal Transduction |
| الوصف: | Oral 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. |
| تدمد: | 1664-3224 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::686f662f26b856981e21c4b5cec40ad2 https://doi.org/10.3389/fimmu.2021.687627 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....686f662f26b856981e21c4b5cec40ad2 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 16643224 |
|---|