title: Regulation of Th1/Th2 polarization by tissue inhibitor of metalloproteinase-3 via modulating dendritic cells.
abstract: Tissue inhibitor of metalloproteinase-3 (TIMP-3) is one of a family of proteins inhibiting matrix metalloproteinases, which has also been identified as a mediator for checking inflammation. Meanwhile, it is well known that inflammation causes the activation of the immune response. However, it is not clear whether TIMP-3 plays a role in the immune system. In the present study, we demonstrated a novel function of TIMP-3 in Th1/Th2 polarization through its influence on the antigen-presenting cells. First, TIMP-3 was found strikingly up-regulated by IL-4 during the differentiation of human dendritic cells via the p38MAPK pathway. Second, the expression of costimulatory molecule-CD86 was repressed by TIMP-3. Besides, the induction of IL-12 in matured dendritic cells was significantly inhibited in a PI3K-dependent manner. Furthermore, dendritic cells matured in the presence of TIMP-3 could stimulate allogeneic naive T helper (Th) cells to display a prominent Th2 polarization. Importantly, in an autoimmune disorder-primary immune thrombocytopenia, TIMP-3 showed a statistically positive correlation with IL-4 and platelet count, but a negative correlation with IFN-γ in patient blood samples. Collectively, these in vitro and in vivo data clearly suggested a novel role of TIMP-3 in Th1/Th2 balance in humans.
authors.affiliation: Institute of Basic Medical Sciences and Key Laboratory of Cardiovascular Proteomics of Shandong Province, Qilu Hospital, Shandong University, Jinan, China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Shao
authors.forename: Hao
authors.initials: H
authors.lastname: Ning
authors.forename: Jiaju
authors.initials: J
authors.lastname: Lv
authors.forename: Yanguo
authors.initials: Y
authors.lastname: Liu
authors.forename: Xin
authors.initials: X
authors.lastname: Zhao
authors.forename: Guangwen
authors.initials: G
authors.lastname: Ren
authors.forename: Alei
authors.initials: A
authors.lastname: Feng
authors.forename: Qi
authors.initials: Q
authors.lastname: Xie
authors.forename: Jintang
authors.initials: J
authors.lastname: Sun
authors.forename: Bingfeng
authors.initials: B
authors.lastname: Song
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Yang
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Gao
authors.forename: Kejia
authors.initials: K
authors.lastname: Ding
authors.forename: Meixiang
authors.initials: M
authors.lastname: Yang
authors.forename: Ming
authors.initials: M
authors.lastname: Hou
authors.forename: Jun
authors.initials: J
authors.lastname: Peng
authors.forename: Xun
authors.initials: X
authors.lastname: Qu
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D016764:Cell Polarity / Q000187:drug effects / Q000235:genetics* / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000097:blood / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D018417:Th1 Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D018418:Th2 Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D055815:Young Adult
chemical_list: D034741:RNA, Small Interfering; C088390:TIMP3 protein, human; D019717:Tissue Inhibitor of Metalloproteinase-3