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TNFAIP8 modulates the survival and immune activity of Th17 cells via p53/ p21/ MDM2 pathway after acute insult

Th17 cells induced immunosuppression plays a vital role in sepsis. As a member of the tumor necrosis factor α induced protein 8 (TNFAIP8) family, TNFAIP8 is associated with different physiopathological conditions with immunological responses. However, its potential roles in regulating Th17 cells aft...

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Detalles Bibliográficos
Autores principales: Cheng, Xiaobin, Shen, Xiaocheng, Wang, Min, Li, Jing, Li, Gang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8803581/
https://www.ncbi.nlm.nih.gov/pubmed/35128379
http://dx.doi.org/10.1016/j.cytox.2022.100062
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author Cheng, Xiaobin
Shen, Xiaocheng
Wang, Min
Li, Jing
Li, Gang
author_facet Cheng, Xiaobin
Shen, Xiaocheng
Wang, Min
Li, Jing
Li, Gang
author_sort Cheng, Xiaobin
collection PubMed
description Th17 cells induced immunosuppression plays a vital role in sepsis. As a member of the tumor necrosis factor α induced protein 8 (TNFAIP8) family, TNFAIP8 is associated with different physiopathological conditions with immunological responses. However, its potential roles in regulating Th17 cells after the acute insult have not been fully elucidated. In this study, sepsis was induced by cecal ligation and puncture (CLP) in the male adult C57BL/6 mice. The stable TNFAIP8 knockdown (KD) Th17 cells were established by infecting with lentivirus carrying TNFAIP8-specific shRNA. CCK-8 assay was conducted to evaluate Th17 cell proliferation, and Annexin V/7-AAD assay was applied for apoptosis measurement by flow cytometry. The alterations of p53/ p21/ MDM2 pathway were assessed by Western blot. We observed that a high TNFAIP8 expression level was related to acute injury in septic mice. TNFAIP8 silencing suppressed Th17 cell proliferation and cytokine production in vivo and in vitro. In addition, TNFAIP8 KD increased Th17 cell apoptosis in septic mice. Furthermore, TNFAIP8 seems to affect the immune function of Th17 cells by regulating p53/ p21/ MDM2 signaling processes. We found that TNFAIP8 KD caused the up-regulation of P21 and MDM2, and also elevated p53 protein level during sepsis. Pharmacological inhibition of p53 partially rescued cell proliferation and apoptotic effects of TNFAIP8 KD. In summary, our work suggests that TNFAIP8 modulates the survival and immune function of Th17 cells after acute insult, which was possibly mediated through the p53/ p21/ MDM2 pathway.
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spelling pubmed-88035812022-02-04 TNFAIP8 modulates the survival and immune activity of Th17 cells via p53/ p21/ MDM2 pathway after acute insult Cheng, Xiaobin Shen, Xiaocheng Wang, Min Li, Jing Li, Gang Cytokine X Research Article Th17 cells induced immunosuppression plays a vital role in sepsis. As a member of the tumor necrosis factor α induced protein 8 (TNFAIP8) family, TNFAIP8 is associated with different physiopathological conditions with immunological responses. However, its potential roles in regulating Th17 cells after the acute insult have not been fully elucidated. In this study, sepsis was induced by cecal ligation and puncture (CLP) in the male adult C57BL/6 mice. The stable TNFAIP8 knockdown (KD) Th17 cells were established by infecting with lentivirus carrying TNFAIP8-specific shRNA. CCK-8 assay was conducted to evaluate Th17 cell proliferation, and Annexin V/7-AAD assay was applied for apoptosis measurement by flow cytometry. The alterations of p53/ p21/ MDM2 pathway were assessed by Western blot. We observed that a high TNFAIP8 expression level was related to acute injury in septic mice. TNFAIP8 silencing suppressed Th17 cell proliferation and cytokine production in vivo and in vitro. In addition, TNFAIP8 KD increased Th17 cell apoptosis in septic mice. Furthermore, TNFAIP8 seems to affect the immune function of Th17 cells by regulating p53/ p21/ MDM2 signaling processes. We found that TNFAIP8 KD caused the up-regulation of P21 and MDM2, and also elevated p53 protein level during sepsis. Pharmacological inhibition of p53 partially rescued cell proliferation and apoptotic effects of TNFAIP8 KD. In summary, our work suggests that TNFAIP8 modulates the survival and immune function of Th17 cells after acute insult, which was possibly mediated through the p53/ p21/ MDM2 pathway. Elsevier 2022-01-18 /pmc/articles/PMC8803581/ /pubmed/35128379 http://dx.doi.org/10.1016/j.cytox.2022.100062 Text en © 2022 Published by Elsevier Ltd. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Article
Cheng, Xiaobin
Shen, Xiaocheng
Wang, Min
Li, Jing
Li, Gang
TNFAIP8 modulates the survival and immune activity of Th17 cells via p53/ p21/ MDM2 pathway after acute insult
title TNFAIP8 modulates the survival and immune activity of Th17 cells via p53/ p21/ MDM2 pathway after acute insult
title_full TNFAIP8 modulates the survival and immune activity of Th17 cells via p53/ p21/ MDM2 pathway after acute insult
title_fullStr TNFAIP8 modulates the survival and immune activity of Th17 cells via p53/ p21/ MDM2 pathway after acute insult
title_full_unstemmed TNFAIP8 modulates the survival and immune activity of Th17 cells via p53/ p21/ MDM2 pathway after acute insult
title_short TNFAIP8 modulates the survival and immune activity of Th17 cells via p53/ p21/ MDM2 pathway after acute insult
title_sort tnfaip8 modulates the survival and immune activity of th17 cells via p53/ p21/ mdm2 pathway after acute insult
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8803581/
https://www.ncbi.nlm.nih.gov/pubmed/35128379
http://dx.doi.org/10.1016/j.cytox.2022.100062
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