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p53 suppresses MHC class II presentation by intestinal epithelium to protect against radiation-induced gastrointestinal syndrome
by
Feng, Zhaohui
, Zhou, Fan
, Liu, Juan
, Bargonetti, Jill
, Yang, Xue
, Chang, Chun-Yuan
, Zhang, Lanjing
, Hu, Wenwei
, Wang, Jianming
, Xie, Ping
in
38/39
/ 631/250/127
/ 631/250/21/324/1508
/ 631/532/2437
/ 631/67/1244
/ 64/60
/ 96/1
/ 96/21
/ 96/31
/ 96/95
/ Animals
/ Antibodies
/ Apoptosis - radiation effects
/ Cell activation
/ Epithelial cells
/ Epithelium
/ Humanities and Social Sciences
/ Inflammation
/ Inflammation - metabolism
/ Interleukin 12
/ Interleukin-12 - metabolism
/ Intestinal Mucosa - metabolism
/ Intestine
/ Irradiation
/ Lymphocytes
/ Lymphocytes T
/ Major histocompatibility complex
/ Mice
/ multidisciplinary
/ p53 Protein
/ Post-irradiation
/ Radiation damage
/ Radiation effects
/ Radiation Injuries - metabolism
/ Radiation therapy
/ Science
/ Science (multidisciplinary)
/ Signal transduction
/ Stem cells
/ Toxicity
/ Tumor suppressor genes
/ Tumor Suppressor Protein p53 - metabolism
/ Tumors
2024
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p53 suppresses MHC class II presentation by intestinal epithelium to protect against radiation-induced gastrointestinal syndrome
by
Feng, Zhaohui
, Zhou, Fan
, Liu, Juan
, Bargonetti, Jill
, Yang, Xue
, Chang, Chun-Yuan
, Zhang, Lanjing
, Hu, Wenwei
, Wang, Jianming
, Xie, Ping
in
38/39
/ 631/250/127
/ 631/250/21/324/1508
/ 631/532/2437
/ 631/67/1244
/ 64/60
/ 96/1
/ 96/21
/ 96/31
/ 96/95
/ Animals
/ Antibodies
/ Apoptosis - radiation effects
/ Cell activation
/ Epithelial cells
/ Epithelium
/ Humanities and Social Sciences
/ Inflammation
/ Inflammation - metabolism
/ Interleukin 12
/ Interleukin-12 - metabolism
/ Intestinal Mucosa - metabolism
/ Intestine
/ Irradiation
/ Lymphocytes
/ Lymphocytes T
/ Major histocompatibility complex
/ Mice
/ multidisciplinary
/ p53 Protein
/ Post-irradiation
/ Radiation damage
/ Radiation effects
/ Radiation Injuries - metabolism
/ Radiation therapy
/ Science
/ Science (multidisciplinary)
/ Signal transduction
/ Stem cells
/ Toxicity
/ Tumor suppressor genes
/ Tumor Suppressor Protein p53 - metabolism
/ Tumors
2024
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p53 suppresses MHC class II presentation by intestinal epithelium to protect against radiation-induced gastrointestinal syndrome
by
Feng, Zhaohui
, Zhou, Fan
, Liu, Juan
, Bargonetti, Jill
, Yang, Xue
, Chang, Chun-Yuan
, Zhang, Lanjing
, Hu, Wenwei
, Wang, Jianming
, Xie, Ping
in
38/39
/ 631/250/127
/ 631/250/21/324/1508
/ 631/532/2437
/ 631/67/1244
/ 64/60
/ 96/1
/ 96/21
/ 96/31
/ 96/95
/ Animals
/ Antibodies
/ Apoptosis - radiation effects
/ Cell activation
/ Epithelial cells
/ Epithelium
/ Humanities and Social Sciences
/ Inflammation
/ Inflammation - metabolism
/ Interleukin 12
/ Interleukin-12 - metabolism
/ Intestinal Mucosa - metabolism
/ Intestine
/ Irradiation
/ Lymphocytes
/ Lymphocytes T
/ Major histocompatibility complex
/ Mice
/ multidisciplinary
/ p53 Protein
/ Post-irradiation
/ Radiation damage
/ Radiation effects
/ Radiation Injuries - metabolism
/ Radiation therapy
/ Science
/ Science (multidisciplinary)
/ Signal transduction
/ Stem cells
/ Toxicity
/ Tumor suppressor genes
/ Tumor Suppressor Protein p53 - metabolism
/ Tumors
2024
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p53 suppresses MHC class II presentation by intestinal epithelium to protect against radiation-induced gastrointestinal syndrome
Journal Article
p53 suppresses MHC class II presentation by intestinal epithelium to protect against radiation-induced gastrointestinal syndrome
2024
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Overview
Radiation-induced gastrointestinal syndrome is a major complication and limiting factor for radiotherapy. Tumor suppressor p53 has a protective role in radiation-induced gastrointestinal toxicity. However, its underlying mechanism remains unclear. Here we report that regulating the IL12-p40/MHC class II signaling pathway is a critical mechanism by which p53 protects against radiation-induced gastrointestinal syndrome. p53 inhibits the expression of inflammatory cytokine IL12-p40, which in turn suppresses the expression of MHC class II on intestinal epithelial cells to suppress T cell activation and inflammation post-irradiation that causes intestinal stem cell damage. Anti-IL12-p40 neutralizing antibody inhibits inflammation and rescues the defects in intestinal epithelial regeneration post-irradiation in p53-deficient mice and prolongs mouse survival. These results uncover that the IL12-p40/MHC class II signaling mediates the essential role of p53 in ensuring intestinal stem cell function and proper immune reaction in response to radiation to protect mucosal epithelium, and suggest a potential therapeutic strategy to protect against radiation-induced gastrointestinal syndrome.
Radiation induced gastrointestinal syndrome is a complication of radiotherapy and the tumor suppressor p53 is implicated in protection from gastrointestinal toxicity. Here Wang and colleagues show that p53 protection against radiation-induced gastrointestinal syndrome involves intestinal stem cell function and inhibition of inflammation triggered by radiation via the IL12- p40/MHC-II axis.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
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