1. Academic Validation
  2. Cholecystokinin octapeptide regulates the differentiation and effector cytokine production of CD4(+) T cells in vitro

Cholecystokinin octapeptide regulates the differentiation and effector cytokine production of CD4(+) T cells in vitro

  • Int Immunopharmacol. 2014 Jun;20(2):307-15. doi: 10.1016/j.intimp.2014.03.013.
Jing-Ge Zhang 1 Jun-Xu Liu 2 Xian-Xian Jia 3 Jing Geng 4 Feng Yu 5 Bin Cong 6
Affiliations

Affiliations

  • 1 Department of Pathophysiology, Institute of Basic Medicine, Hebei Medical University, Shijiazhuang, China. Electronic address: [email protected].
  • 2 Department of Laboratory Animal Science, Hebei Medical University, Hebei Key Lab of Laboratory Animal Science, Shijiazhuang, China. Electronic address: [email protected].
  • 3 Hebei Key Laboratory of Forensic Medicine, Hebei Medical University, Shijiazhuang, China. Electronic address: [email protected].
  • 4 Hebei Key Laboratory of Forensic Medicine, Hebei Medical University, Shijiazhuang, China. Electronic address: [email protected].
  • 5 Hebei Key Laboratory of Forensic Medicine, Hebei Medical University, Shijiazhuang, China. Electronic address: [email protected].
  • 6 Hebei Key Laboratory of Forensic Medicine, Hebei Medical University, Shijiazhuang, China. Electronic address: [email protected].
Abstract

Cholecystokinin octapeptide (CCK-8), an immunomodulatory peptide, can promote or suppress the development or function of specific CD4(+) T cell subsets by regulating antigen-presenting cell functions. In the current study, we investigated whether CCK-8 exerts a direct effect on T cells through influencing differentiation and cytokine production of distinct CD4(+) T cell subsets in vitro. Our results showed that CCK-8 differentially affects the development and function of CD4(+) T cell populations, with a negative influence on Th1 and Th17 cells and positive regulatory effect on inducible T regulatory cells (iTreg). Notably, CCK-8 suppressed Th1 while slightly enhancing Th2 development and cytokine production. Similarly, CCK-8 inhibited the differentiation of Th17 cells and promoted Foxp3 expression. L-364,718 and LY-288,513, selective antagonists of CCK1R and CCK2R, respectively, suppressed the effects of CCK-8 on CD4(+) T cell subset-specific transcription factors. Our findings strongly indicate that CCK-8 exerts a direct effect on T cells, which is dependent on CCKRs, particularly CCK2R. The collective results aid in further clarifying the mechanism underlying the anti-inflammatory and immunoregulatory effects of CCK-8.

Keywords

Cholecystokinin; Signature cytokines; T helper cells; Transcription factors.

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