Interleukin‐6 receptor alpha and CD27 discriminate intratumoral T helper 17 subpopulations with distinct functional properties in a mouse lung cancer model

Abstract Background T helper 17 (Th17) cells actively participate in the tumor immune response in lung cancer. However, the heterogeneity and plasticity of intratumoral Th17 cells in lung cancer remain elusive. In this study, Th17 subpopulations were characterized in a mouse lung cancer model. Metho...

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Autores principales:	Chong Liu, Fei Xiong, Lingying Wang, Kang Chen, Pingshang Wu, Li Hua, Zhuo Zhang
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	CD27 interleukin‐6 receptor alpha chain lung cancer T helper 17 cells Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/3156429135d2468e9a37d82ad059df42
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spelling	oai:doaj.org-article:3156429135d2468e9a37d82ad059df422021-11-12T19:57:15ZInterleukin‐6 receptor alpha and CD27 discriminate intratumoral T helper 17 subpopulations with distinct functional properties in a mouse lung cancer model2050-452710.1002/iid3.533https://doaj.org/article/3156429135d2468e9a37d82ad059df422021-12-01T00:00:00Zhttps://doi.org/10.1002/iid3.533https://doaj.org/toc/2050-4527Abstract Background T helper 17 (Th17) cells actively participate in the tumor immune response in lung cancer. However, the heterogeneity and plasticity of intratumoral Th17 cells in lung cancer remain elusive. In this study, Th17 subpopulations were characterized in a mouse lung cancer model. Methods Urethane was administered to induce lung cancer in interleukin (IL)‐17‐EGFP transgenic mice. Flow cytometry was used to analyze the phenotypes, signaling status, and functions of Th17 subpopulations either in vivo or in vitro. The adoptive transfer assay and real‐time polymerase chain reaction were applied to analyze the plasticity of Th17 subpopulations. Results IL‐6RαhighCD27− Th17 and IL‐6RαlowCD27+ Th17 were identified in intratumoral Th17 cells. The two subpopulations expressed equivalent RORγt. However, the former expressed higher T‐bet but lower Foxp3, more IL‐17A and IFN‐γ but less IL‐10 than the latter. Furthermore, IL‐6RαhighCD27− Th17 moderately inhibited the proliferation of lung cancer cells while IL‐6RαlowCD27+ Th17 could not. IL‐6RαhighCD27− Th17 exhibited weaker Jun N‐terminal kinases (JNK) signaling but stronger signal transducer and activator of transcription 3 (Stat3) signaling than IL‐6RαlowCD27+ Th17. The adoptive transfer assay indicated that both subpopulations downregulated RORγt in recipients' spleens but maintained RORγt in recipients' lungs. Meanwhile, IL‐6RαhighCD27− Th17 expressed higher T‐bet and IFN‐γ than IL‐6RαlowCD27+ Th17 in the recipients. IL‐6RαlowCD27+ Th17 expressed Foxp3 and IL‐10 in recipients' spleens but not lungs. Conclusions This study reveals intratumoral Th17 subpopulations with distinct functional properties and signaling patterns, thus offering valuable insight into Th17 heterogeneity and plasticity in lung cancer.Chong LiuFei XiongLingying WangKang ChenPingshang WuLi HuaZhuo ZhangWileyarticleCD27interleukin‐6 receptor alpha chainlung cancerT helper 17 cellsImmunologic diseases. AllergyRC581-607ENImmunity, Inflammation and Disease, Vol 9, Iss 4, Pp 1749-1758 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	CD27 interleukin‐6 receptor alpha chain lung cancer T helper 17 cells Immunologic diseases. Allergy RC581-607
spellingShingle	CD27 interleukin‐6 receptor alpha chain lung cancer T helper 17 cells Immunologic diseases. Allergy RC581-607 Chong Liu Fei Xiong Lingying Wang Kang Chen Pingshang Wu Li Hua Zhuo Zhang Interleukin‐6 receptor alpha and CD27 discriminate intratumoral T helper 17 subpopulations with distinct functional properties in a mouse lung cancer model
description	Abstract Background T helper 17 (Th17) cells actively participate in the tumor immune response in lung cancer. However, the heterogeneity and plasticity of intratumoral Th17 cells in lung cancer remain elusive. In this study, Th17 subpopulations were characterized in a mouse lung cancer model. Methods Urethane was administered to induce lung cancer in interleukin (IL)‐17‐EGFP transgenic mice. Flow cytometry was used to analyze the phenotypes, signaling status, and functions of Th17 subpopulations either in vivo or in vitro. The adoptive transfer assay and real‐time polymerase chain reaction were applied to analyze the plasticity of Th17 subpopulations. Results IL‐6RαhighCD27− Th17 and IL‐6RαlowCD27+ Th17 were identified in intratumoral Th17 cells. The two subpopulations expressed equivalent RORγt. However, the former expressed higher T‐bet but lower Foxp3, more IL‐17A and IFN‐γ but less IL‐10 than the latter. Furthermore, IL‐6RαhighCD27− Th17 moderately inhibited the proliferation of lung cancer cells while IL‐6RαlowCD27+ Th17 could not. IL‐6RαhighCD27− Th17 exhibited weaker Jun N‐terminal kinases (JNK) signaling but stronger signal transducer and activator of transcription 3 (Stat3) signaling than IL‐6RαlowCD27+ Th17. The adoptive transfer assay indicated that both subpopulations downregulated RORγt in recipients' spleens but maintained RORγt in recipients' lungs. Meanwhile, IL‐6RαhighCD27− Th17 expressed higher T‐bet and IFN‐γ than IL‐6RαlowCD27+ Th17 in the recipients. IL‐6RαlowCD27+ Th17 expressed Foxp3 and IL‐10 in recipients' spleens but not lungs. Conclusions This study reveals intratumoral Th17 subpopulations with distinct functional properties and signaling patterns, thus offering valuable insight into Th17 heterogeneity and plasticity in lung cancer.
format	article
author	Chong Liu Fei Xiong Lingying Wang Kang Chen Pingshang Wu Li Hua Zhuo Zhang
author_facet	Chong Liu Fei Xiong Lingying Wang Kang Chen Pingshang Wu Li Hua Zhuo Zhang
author_sort	Chong Liu
title	Interleukin‐6 receptor alpha and CD27 discriminate intratumoral T helper 17 subpopulations with distinct functional properties in a mouse lung cancer model
title_short	Interleukin‐6 receptor alpha and CD27 discriminate intratumoral T helper 17 subpopulations with distinct functional properties in a mouse lung cancer model
title_full	Interleukin‐6 receptor alpha and CD27 discriminate intratumoral T helper 17 subpopulations with distinct functional properties in a mouse lung cancer model
title_fullStr	Interleukin‐6 receptor alpha and CD27 discriminate intratumoral T helper 17 subpopulations with distinct functional properties in a mouse lung cancer model
title_full_unstemmed	Interleukin‐6 receptor alpha and CD27 discriminate intratumoral T helper 17 subpopulations with distinct functional properties in a mouse lung cancer model
title_sort	interleukin‐6 receptor alpha and cd27 discriminate intratumoral t helper 17 subpopulations with distinct functional properties in a mouse lung cancer model
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/3156429135d2468e9a37d82ad059df42
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Interleukin‐6 receptor alpha and CD27 discriminate intratumoral T helper 17 subpopulations with distinct functional properties in a mouse lung cancer model

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