CD147/basigin limits lupus nephritis and Th17 cell differentiation in mice by inhibiting the interleukin-6/STAT-3 pathway

Kayaho Maeda, Tomoki Kosugi, Waichi Sato, Hiroshi Kojima, Yuka Sato, Daisuke Kamimura, Noritoshi Kato, Naotake Tsuboi, Yukio Yuzawa, Seiichi Matsuo, Masaaki Murakami, Shoichi Maruyama, Kenji Kadomatsu

Research output: Contribution to journalArticle

10 Citations (Scopus)

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. Conclusion Bsg plays an indispensable role in Th17 cell differentiation as a negative regulator by suppressing the IL-6/STAT-3 pathway.

Original languageEnglish
Pages (from-to)2185-2195
Number of pages11
JournalArthritis and Rheumatology
Volume67
Issue number8
DOIs
Publication statusPublished - 01-08-2015

Fingerprint

CD147 Antigens
Th17 Cells
Lupus Nephritis
Cell Differentiation
Interleukin-17
mouse interleukin-6
T-Lymphocytes
Phosphorylation
Kidney
Th1 Cells

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Rheumatology
  • Immunology

Cite this

Maeda, Kayaho ; Kosugi, Tomoki ; Sato, Waichi ; Kojima, Hiroshi ; Sato, Yuka ; Kamimura, Daisuke ; Kato, Noritoshi ; Tsuboi, Naotake ; Yuzawa, Yukio ; Matsuo, Seiichi ; Murakami, Masaaki ; Maruyama, Shoichi ; Kadomatsu, Kenji. / CD147/basigin limits lupus nephritis and Th17 cell differentiation in mice by inhibiting the interleukin-6/STAT-3 pathway. In: Arthritis and Rheumatology. 2015 ; Vol. 67, No. 8. pp. 2185-2195.
@article{54a37151e912443492f7a2e33fbc240f,
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. Conclusion Bsg plays an indispensable role in Th17 cell differentiation as a negative regulator by suppressing the IL-6/STAT-3 pathway.",
author = "Kayaho Maeda and Tomoki Kosugi and Waichi Sato and Hiroshi Kojima and Yuka Sato and Daisuke Kamimura and Noritoshi Kato and Naotake Tsuboi and Yukio Yuzawa and Seiichi Matsuo and Masaaki Murakami and Shoichi Maruyama and Kenji Kadomatsu",
year = "2015",
month = "8",
day = "1",
doi = "10.1002/art.39155",
language = "English",
volume = "67",
pages = "2185--2195",
journal = "Arthritis and Rheumatology",
issn = "2326-5191",
publisher = "John Wiley and Sons Ltd",
number = "8",

}

Maeda, K, Kosugi, T, Sato, W, Kojima, H, Sato, Y, Kamimura, D, Kato, N, Tsuboi, N, Yuzawa, Y, Matsuo, S, Murakami, M, Maruyama, S & Kadomatsu, K 2015, 'CD147/basigin limits lupus nephritis and Th17 cell differentiation in mice by inhibiting the interleukin-6/STAT-3 pathway', Arthritis and Rheumatology, vol. 67, no. 8, pp. 2185-2195. https://doi.org/10.1002/art.39155

CD147/basigin limits lupus nephritis and Th17 cell differentiation in mice by inhibiting the interleukin-6/STAT-3 pathway. / Maeda, Kayaho; Kosugi, Tomoki; Sato, Waichi; Kojima, Hiroshi; Sato, Yuka; Kamimura, Daisuke; Kato, Noritoshi; Tsuboi, Naotake; Yuzawa, Yukio; Matsuo, Seiichi; Murakami, Masaaki; Maruyama, Shoichi; Kadomatsu, Kenji.

In: Arthritis and Rheumatology, Vol. 67, No. 8, 01.08.2015, p. 2185-2195.

Research output: Contribution to journalArticle

TY - JOUR

T1 - CD147/basigin limits lupus nephritis and Th17 cell differentiation in mice by inhibiting the interleukin-6/STAT-3 pathway

AU - Maeda, Kayaho

AU - Kosugi, Tomoki

AU - Sato, Waichi

AU - Kojima, Hiroshi

AU - Sato, Yuka

AU - Kamimura, Daisuke

AU - Kato, Noritoshi

AU - Tsuboi, Naotake

AU - Yuzawa, Yukio

AU - Matsuo, Seiichi

AU - Murakami, Masaaki

AU - Maruyama, Shoichi

AU - Kadomatsu, Kenji

PY - 2015/8/1

Y1 - 2015/8/1

N2 - 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. Conclusion Bsg plays an indispensable role in Th17 cell differentiation as a negative regulator by suppressing the IL-6/STAT-3 pathway.

AB - 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. Conclusion Bsg plays an indispensable role in Th17 cell differentiation as a negative regulator by suppressing the IL-6/STAT-3 pathway.

UR - http://www.scopus.com/inward/record.url?scp=84938152009&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84938152009&partnerID=8YFLogxK

U2 - 10.1002/art.39155

DO - 10.1002/art.39155

M3 - Article

C2 - 25891969

AN - SCOPUS:84938152009

VL - 67

SP - 2185

EP - 2195

JO - Arthritis and Rheumatology

JF - Arthritis and Rheumatology

SN - 2326-5191

IS - 8

ER -