title: CD147/basigin limits lupus nephritis and Th17 cell differentiation in mice by inhibiting the interleukin-6/STAT-3 pathway.
abstract: OBJECTIVE
  Interleukin-17 (IL-17)-producing T cells (Th17 cells) play critical roles in the pathogenesis of immune-related diseases, including systemic lupus erythematosus. However, the fundamental mechanism regulating Th17 cell differentiation is not fully understood. Recently, we demonstrated that plasma levels of CD147/basigin (Bsg) in patients with lupus nephritis (LN) were closely associated with disease activity. but the molecular mechanism involving Bsg has been elusive. Here, we addressed the role of Bsg in the pathogenesis of LN.
  
  
  METHODS
  Injections of pristane (2,6,10,14-tetramethylpentadecane [TMPD]) were administered to Bsg(-/-) or Bsg(+/+) mice to induce LN. The mice were killed 6 months after being injected, for histologic and biochemical analyses of the kidneys and spleens.
  
  
  RESULTS
  Pristane induced LN more strikingly in Bsg(-/-) mice than in Bsg(+/+) mice, even though humoral autoimmunity was similarly increased in both genotypes. The increased number of Th17, but not Th1, Treg cells, was augmented in Bsg(-/-) mice. The expression of IL-17 was also increased in the kidneys of Bsg(-/-) mice, in proportion to LN disease activity. Furthermore, treatment with anti-IL-17 antibody reduced LN disease activity in Bsg(-/-) mice. Complementary to these phenotypes of Bsg(-/-) mice, Bsg expression was enhanced in activated CD4+ T cells in vivo and in vitro. Bsg deficiency selectively augmented in vitro differentiation of naive CD4+ T cells to Th17 cells and STAT-3 phosphorylation during this differentiation. Moreover, STAT-3 phosphorylation was suppressed by crosslinking of Bsg with its antibody.
  
  
  CONCLUSIONS
  Bsg plays an indispensable role in Th17 cell differentiation as a negative regulator by suppressing the IL-6/STAT-3 pathway.
authors.affiliation: Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Kayaho
authors.initials: K
authors.lastname: Maeda
authors.affiliation: Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Kosugi
authors.affiliation: Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Waichi
authors.initials: W
authors.lastname: Sato
authors.affiliation: Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kojima
authors.affiliation: Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kamimura
authors.affiliation: Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Noritoshi
authors.initials: N
authors.lastname: Kato
authors.affiliation: Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Naotake
authors.initials: N
authors.lastname: Tsuboi
authors.affiliation: Fujita Health University School of Medicine, Toyoake, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Yuzawa
authors.affiliation: Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Seiichi
authors.initials: S
authors.lastname: Matsuo
authors.affiliation: Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Murakami
authors.affiliation: Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Shoichi
authors.initials: S
authors.lastname: Maruyama
authors.affiliation: Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kadomatsu
mesh_terms: D000818:Animals; D051926:Basigin / Q000235:genetics / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology*; D015850:Interleukin-6 / Q000276:immunology* / Q000378:metabolism; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008181:Lupus Nephritis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D050796:STAT3 Transcription Factor / Q000276:immunology*; D015398:Signal Transduction; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism
chemical_list: C497887:Bsg protein, mouse; D015850:Interleukin-6; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D051926:Basigin