title: Curcumin inhibiting Th17 cell differentiation by regulating the metabotropic glutamate receptor-4 expression on dendritic cells.
abstract: Th17 cells have been categorized as a new lineage of CD4+ T cells, and played a crucial role in the pathogenesis of numerous autoimmune disorders. Type 4 metabotropic glutamate receptor (mGluR4), a member of group III mGluRs, recently has been found to be expressed in many types of immune cells and mediate adaptive immunity. Curcumin has been shown to exhibit potent anti-inflammatory, antimutagenic and anticarcinogenic properties. For the past few years, it has gradually been regarded as an pluripotent immunomodulatory agent that can regulate the activation of immune cells. In the present study, we investigated the efficacy and mechanism of curcumin on Th17 cells. Treatment with curcumin significantly reduced IL-6 and IL-23 production by dendritic cells (DC). Additionally, it had a dramatic reduction in the proliferation of CD4+ T cells co-cultured with DC. Furthermore, expression of the Th17 cells related cytokine profiles (IL-17A and RORγt) was dramatically decreased in curcumin-treated groups. These findings indicated that curcumin inhibited the differentiation and development of Th17 cells. Besides, we found that mGluR4 was constitutively expressed in mouse bone marrow derived DC (BMDC) for the first time. In addition, mGluR4 siRNA-transfected BMDC tipped the balance of T cell differentiation in favor of the Th17 phenotype. We first reported that curcumin increased the mGluR4 expression in mouse BMDC activated with LPS, which likely contributed to the mechanism of inhibiting the Th17 cell differentiation. Our findings suggest that curcumin might be a potential candidate for Th17 related autoimmune disorders.
authors.affiliation: Department of Dermatology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, PR China.
authors.forename: Guangming
authors.initials: G
authors.lastname: Zhao
authors.affiliation: Department of Dermatology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Dermatology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, PR China.
authors.forename: Xiaying
authors.initials: X
authors.lastname: Yi
authors.affiliation: Department of Dermatology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, PR China.
authors.forename: Yupeng
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Dermatology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, PR China.
authors.forename: Song
authors.initials: S
authors.lastname: Qiao
authors.affiliation: Department of Dermatology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, PR China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Dermatology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Ni
authors.affiliation: Department of Dermatology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, PR China. Electronic address: szqdalian@163.com.
authors.forename: Zhiqi
authors.initials: Z
authors.lastname: Song
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001327:Autoimmune Diseases / Q000188:drug therapy*; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D003474:Curcumin / Q000627:therapeutic use*; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D034741:RNA, Small Interfering / Q000235:genetics; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics / Q000378:metabolism*; D058504:Th17 Cells / Q000187:drug effects* / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D008070:Lipopolysaccharides; D034741:RNA, Small Interfering; D018094:Receptors, Metabotropic Glutamate; D003474:Curcumin; C108823:metabotropic glutamate receptor 4
keywords: Curcumin; Dendritic cells; Metabotropic glutamate receptor-4; Th17 cells