Hyperactivation of gp130-mediated STAT3 signaling induces a rheumatoid arthritis-like disease that is dependent on MHC class II restricted CD4+ T cells

Masaaki Murakami, Shinichiro Sawa, Daisuke Kamimura, Hokuto Kamon, Hidemitsu Kitamura, Takaya Kawabe, Park Sung-Joo, Katsuhiko Ishihara, Toshio Hirano

Research output: Contribution to journalArticle

Abstract

Mice having a point mutation of IL-6 signal transducer, gp130, named gp130F759 induced a rheumatoid arthritis-like disease. The disease induction is totally dependent on mature lymphocytes, since no arthritis-like disease induced in a double mutant between gp130F759 and RAG2KO mice. We prepared several other double mutants including gp130F759/IgMKO, gp130F759/CD8KO, gp130F759/CIITAKO and gp130F759/CD4KO and analyzed the development of the arthritis. We found that development of the disease attenuated in gp130F759/CIITAKO and gp130F759/CD4KO, suggesting the MHC class II-restricted CD4+ T cells are important for the disease development. We showed memory/activated phenotype of CD4+ T cells increased in gp130F759 mice. Since activation of CD4+ T cells is mainly controlled by dendritic cells (DC) in vivo, we investigated this feature of DC in gp130F759 mice. We isolated DCs from superficial lymph nodes and observed that IL-6-mediated signaling suppresses maturation of DCs in vivo. However, total number of DCs in vivo significantly increased in gp130F759 mice compared with wild type controls. Thus, we hypothesize that the rheumatoid arthritis-like disease in gp130F759 mice is induced by an interaction between CD4+ T cells and DC under gp130F759 signal regulation.

Original languageEnglish
Pages (from-to)207-211
Number of pages5
JournalInternational Congress Series
Volume1285
DOIs
Publication statusPublished - Nov 1 2005
Externally publishedYes

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Rheumatoid Arthritis
T-Lymphocytes
Dendritic Cells
Arthritis
Interleukin-6
Cytokine Receptor gp130
Point Mutation
Lymph Nodes
Lymphocytes
Phenotype

All Science Journal Classification (ASJC) codes

  • Medicine(all)

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Hyperactivation of gp130-mediated STAT3 signaling induces a rheumatoid arthritis-like disease that is dependent on MHC class II restricted CD4+ T cells. / Murakami, Masaaki; Sawa, Shinichiro; Kamimura, Daisuke; Kamon, Hokuto; Kitamura, Hidemitsu; Kawabe, Takaya; Sung-Joo, Park; Ishihara, Katsuhiko; Hirano, Toshio.

In: International Congress Series, Vol. 1285, 01.11.2005, p. 207-211.

Research output: Contribution to journalArticle

Murakami, Masaaki ; Sawa, Shinichiro ; Kamimura, Daisuke ; Kamon, Hokuto ; Kitamura, Hidemitsu ; Kawabe, Takaya ; Sung-Joo, Park ; Ishihara, Katsuhiko ; Hirano, Toshio. / Hyperactivation of gp130-mediated STAT3 signaling induces a rheumatoid arthritis-like disease that is dependent on MHC class II restricted CD4+ T cells. In: International Congress Series. 2005 ; Vol. 1285. pp. 207-211.
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