Cholecystokinin octapeptide regulates the differentiation and effector cytokine production of CD4(+) T cells in vitro.
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.
Department of Pathophysiology, Institute of Basic Medicine, Hebei Medical University, Shijiazhuang, China. Electronic address: zhangjg001@163.com.
Jing-Ge
JG
Zhang
Department of Laboratory Animal Science, Hebei Medical University, Hebei Key Lab of Laboratory Animal Science, Shijiazhuang, China. Electronic address: liujx6688@sina.com.
Jun-Xu
JX
Liu
Hebei Key Laboratory of Forensic Medicine, Hebei Medical University, Shijiazhuang, China. Electronic address: pigejxx@qq.com.
Xian-Xian
XX
Jia
Hebei Key Laboratory of Forensic Medicine, Hebei Medical University, Shijiazhuang, China. Electronic address: 46232839@qq.com.
Jing
J
Geng
Hebei Key Laboratory of Forensic Medicine, Hebei Medical University, Shijiazhuang, China. Electronic address: fengyu@hebmu.edu.cn.
Feng
F
Yu
Hebei Key Laboratory of Forensic Medicine, Hebei Medical University, Shijiazhuang, China. Electronic address: hbydbincong@126.com.
Bin
B
Cong
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D020109:Devazepide / Q000494:pharmacology; D051858:Forkhead Transcription Factors / Q000378:metabolism; D066298:In Vitro Techniques; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D011720:Pyrazoles / Q000494:pharmacology; D043886:Receptor, Cholecystokinin A / Q000037:antagonists & inhibitors; D043887:Receptor, Cholecystokinin B / Q000037:antagonists & inhibitors; D012844:Sincalide / Q000494:pharmacology*; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology; D058504:Th17 Cells / Q000187:drug effects* / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology
D000893:Anti-Inflammatory Agents; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D011720:Pyrazoles; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; C074681:1-(4-bromophenylaminocarbonyl)-4,5-diphenyl-3-pyrazolidinone; D020109:Devazepide; D012844:Sincalide
Cholecystokinin; Signature cytokines; T helper cells; Transcription factors