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IL‐10 promotes malignant pleural effusion in mice by regulating T H 1‐ and T H 17‐cell differentiation and migration
- Source :
- European Journal of Immunology. 49:653-665
- Publication Year :
- 2019
- Publisher :
- Wiley, 2019.
-
Abstract
- The role of IL-10 in malignant pleural effusion (MPE) remains unknown. By using murine MPE models, we observed that an increase in pleural IL-10 was a significant predictor of increased risk of death. We noted that TH 1- and TH 17-cell content in MPE was higher in IL-10-/- mice than in WT mice, and IL-10 deficiency promoted differentiation into TH 1 but not into TH 17 cells. A higher fraction of TH 1 and TH 17 cells in the MPE of IL-10-/- mice expressed CXCR3 compared with WT mice. We also demonstrated that Lewis lung cancer and colon adenocarcinoma cells secreted large amounts of CXCL10, a ligand of CXCR3, which induced the migration of TH 1 and TH 17 cells into the MPE, and IFN-γ could promote this signaling cascade. Furthermore, intrapleural injection of mice with CXCL10-deficient tumor cells led to decreased TH 1- and TH 17-cell content in MPE, increased MPE volume, and reduced survival of MPE-bearing mice. Taken together, we demonstrated that IL-10 deficiency promoted T-cell differentiation into TH 1 cells and upregulated the CXCR3-CXCL10 signaling pathway that recruits TH 1 and TH 17 cells into MPE, ultimately resulting in decreased MPE formation and longer survival time of mice-bearing MPE.
- Subjects :
- 0301 basic medicine
Cellular differentiation
Immunology
Biology
CXCR3
medicine.disease
03 medical and health sciences
Interleukin 10
030104 developmental biology
0302 clinical medicine
Downregulation and upregulation
medicine
Cancer research
Immunology and Allergy
CXCL10
Malignant pleural effusion
Signal transduction
Lung cancer
030215 immunology
Subjects
Details
- ISSN :
- 15214141 and 00142980
- Volume :
- 49
- Database :
- OpenAIRE
- Journal :
- European Journal of Immunology
- Accession number :
- edsair.doi...........fe06ece91cebbe13e3bb3e35fd7ae483