title: Functional modulation of the pathway between dendritic cells (DCs) and CD4+T cells by the neuropeptide: methionine enkephalin (MENK).
abstract: MENK, the endogenous neuropeptide, is suggested to be involved in the regulatory loop between the immune and neuroendocrine systems, with modulation of various functions of cells related to both the innate and adaptive immune systems. Our present research findings show that MENK serves as an immune modulator to the pathway between DCs and CD4+T cells. We studied changes of DCs in key surface molecules, the activity of acid phosphatases (ACPs), the production of IL-12, and the effects on murine CD4+T cell expansion and their cytokine production by MENK alone, and in combination with interleukin-2 (IL-2) or interferon-γ (IFN-γ). In fact, we found that MENK could markedly induce the maturation of DCs through the addition of surface molecules such as MHC class II, CD86, and CD40 on murine DCs, the production of IL-12, and the down-regulation of ACP inside DCs, (which occurs when phagocytosis of DCs is decreased, and antigen presentation increased with maturation). We also found that MENK alone or in combination with IL-2 or IFN-γ, could markedly up-regulate both CD4+T cell expansion and the CD4 molecule expression in vivo and in vitro and that MENK alone, or MENK+IL-2, could enhance the production of interferon-γ from CD4+T cells. Moreover, MENK alone, or MENK+IFN-γ, could enhance the production of IL-2 from CD4+T cells. It is therefore concluded that MENK can exert positive modulation to the pathway between dendritic cells and CD4+T cells.
authors.affiliation: Department of Immunology, School of Basic Medical Science, China Medical University, No. 92, North Second Road, Heping District, Shenyang 110001, PR China. fpshan@mail.cmu.edu.cn
authors.forename: Fengping
authors.initials: F
authors.lastname: Shan
authors.forename: Yanjie
authors.initials: Y
authors.lastname: Xia
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.forename: Jingjuan
authors.initials: J
authors.lastname: Meng
authors.forename: Changlong
authors.initials: C
authors.lastname: Lu
authors.forename: Yiming
authors.initials: Y
authors.lastname: Meng
authors.forename: Nicolas P
authors.initials: NP
authors.lastname: Plotnikoff
mesh_terms: D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism*; D002460:Cell Line; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism*; D004744:Enkephalin, Methionine / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D018664:Interleukin-12 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009479:Neuropeptides / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D007376:Interleukin-2; D009479:Neuropeptides; D012333:RNA, Messenger; D018664:Interleukin-12; D004744:Enkephalin, Methionine; D000135:Acid Phosphatase