2. Academic Validation
  3. C5a enhances inflammation and chemotaxis of γδ T cells in malignant pleural effusion

C5a enhances inflammation and chemotaxis of γδ T cells in malignant pleural effusion

  • Int Immunopharmacol. 2023 Dec 9:127:111332. doi: 10.1016/j.intimp.2023.111332.
Shuanglinzi Deng 1,  Yuanyuan Jiang 2,  Lisha Luo 1,  Huan Tang 1,  Xinyue Hu 1,  Chendong Wu 1,  Jiale Tang 1,  Huan Ge 1,  Xiaoxiao Gong 1,  Runjin Cai 1,  Guo Wang 1,  Xiaozhao Li 3,  Juntao Feng 4
Affiliations

Affiliations

  • 1 Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China.
  • 2 Department of Clinical Laboratory, Xiangya Hospital, Central South University, Changsha, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China.
  • 3 Department of Nephrology, Xiangya Hospital, Central South University, Changsha, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China. Electronic address: lixiaozhao@csu.edu.cn.
  • 4 Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China. Electronic address: jtfeng1976@csu.edu.cn.
PMID: 38071913 DOI: 10.1016/j.intimp.2023.111332
Abstract

Background: The inhibitory effect of γδT17 cells on the formation of murine malignant pleural effusions (MPE) has been established. However, there is limited understanding regarding the phenotypic characterization of γδ T cells in MPE patients and their recruitment to the pleural cavity.

Methods: We quantified γδ T cell prevalence in pleural effusions and corresponding peripheral blood from malignant and benign patients using immunohistochemistry and flow cytometry. The expression of effector memory phenotype, stimulatory/inhibitory/chemokine receptors and cytokines on γδ T cells in MPE was analyzed using multicolor flow cytometry. The infiltration of γδ T cells in MPE was assessed through immunofluorescence, ELISA, flow cytometry and transwell migration assay.

Results: We observed a significant infiltration of γδ T cells in MPE, surpassing the levels found in blood and benign pleural effusion. γδ T cells in MPE exhibited heightened expression of CD56 and an effector memory phenotype, while displaying lower levels of PD-1. Furthermore, γδ T cells in MPE showed higher levels of cytokines (IFN-γ, IL-17A and IL-22) and chemokine receptors (CCR2, CCR5 and CCR6). CCR2 expression was notably higher in the Vδ2 subtype compared to Vδ1 cells. Moreover, the complement C5a enhanced cytokine release by γδ T cells, upregulated CCR2 expression in Vδ2 subsets, and stimulated the production of chemokines (CCL2, CCL7 and CCL20) in MPE. In vitro utilizing CCR2 neutralising and C5aR antagonist significantly reduced the recruitment of γδ T cells.

Conclusions: γδ T cells infiltrate MPE by overexpressing CCR2 and exhibit hightened inflammation, which is further augmented by C5a.

Keywords

C5a; Malignant pleural effusion; γδ T cells.

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