Interleukin‐6 receptor alpha and CD27 discriminate intratumoral T helper 17 subpopulations with distinct functional properties in a mouse lung cancer model Article Swipe
Chong Liu
,
Fei Xiong
,
Lingying Wang
,
Kang Chen
,
Ping-Shang Wu
,
Li Hua
,
Zhuo Zhang
·
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.1002/iid3.533
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.1002/iid3.533
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‐6Rα high CD27 − Th17 and IL‐6Rα low CD27 + 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‐6Rα high CD27 − Th17 moderately inhibited the proliferation of lung cancer cells while IL‐6Rα low CD27 + Th17 could not. IL‐6Rα high CD27 − Th17 exhibited weaker Jun N‐terminal kinases (JNK) signaling but stronger signal transducer and activator of transcription 3 (Stat3) signaling than IL‐6Rα low CD27 + Th17. The adoptive transfer assay indicated that both subpopulations downregulated RORγt in recipients' spleens but maintained RORγt in recipients' lungs. Meanwhile, IL‐6Rα high CD27 − Th17 expressed higher T‐bet and IFN‐γ than IL‐6Rα low CD27 + Th17 in the recipients. IL‐6Rα low CD27 + 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.
Related Topics
Concepts
RAR-related orphan receptor gamma
FOXP3
STAT3
Interleukin 17
Adoptive cell transfer
STAT protein
Flow cytometry
Cancer research
Lung cancer
Immune system
IL-2 receptor
Immunology
Interleukin
Biology
Chemistry
Molecular biology
Signal transduction
T cell
Cytokine
Cell biology
Medicine
Internal medicine
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1002/iid3.533
- OA Status
- gold
- Cited By
- 1
- References
- 18
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W3203980559
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W3203980559Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1002/iid3.533Digital Object Identifier
- Title
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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 modelWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2021Year of publication
- Publication date
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2021-09-27Full publication date if available
- Authors
-
Chong Liu, Fei Xiong, Lingying Wang, Kang Chen, Ping-Shang Wu, Li Hua, Zhuo ZhangList of authors in order
- Landing page
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https://doi.org/10.1002/iid3.533Publisher landing page
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YesWhether a free full text is available
- OA status
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goldOpen access status per OpenAlex
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https://doi.org/10.1002/iid3.533Direct OA link when available
- Concepts
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RAR-related orphan receptor gamma, FOXP3, STAT3, Interleukin 17, Adoptive cell transfer, STAT protein, Flow cytometry, Cancer research, Lung cancer, Immune system, IL-2 receptor, Immunology, Interleukin, Biology, Chemistry, Molecular biology, Signal transduction, T cell, Cytokine, Cell biology, Medicine, Internal medicineTop concepts (fields/topics) attached by OpenAlex
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1Total citation count in OpenAlex
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10Other works algorithmically related by OpenAlex
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| sustainable_development_goals[0].display_name | Reduced inequalities |
| citation_normalized_percentile.value | 0.41580296 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |