Fibroblasts stimulated via HLA-II molecules produce prostaglandin E 2 and regulate cytokine production from helper T cells

Nahoko Kato-Kogoe, Hideki Ohyama, Fusanori Nishimura, Michio Meguro, Sayuri Yoshizawa, Yuka Okada, Keiji Nakasho, Koji Yamanegi, Naoko Yamada, Masaki Hata, Takehiro Higashi, Nobuyuki Terada, Sho Matsushita

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Fibroblasts act as important immune regulatory cells via their ability to cross-talk with T cells accumulating in lesions. Our previous study showed that fibroblasts produce several cytokines and chemokines by crosslinking HLA class II (HLA-II) molecules with monoclonal antibodies or by making T-cell receptor-peptide-HLA complexes. It is thus conceivable that the interaction of T cells and fibroblasts via HLA-II affects fibroblast responses to stimuli. This study used human gingival fibroblasts (HGF) to investigate possible effects of these fibroblast-derived soluble factors on the differentiation of nave T cells and on the subsequent fibroblast responses. After mixed lymphocyte reaction culture between nave T cells and allogeneic dendritic cells in the presence of culture supernatant from HGF stimulated via HLA-DQ molecules (DQ-sup), but not via DR, T cells exhibited a Th2-shifted phenotype, thereby producing quantitatively more IL-13 and IL-5 compared with interferon-γ. Astonishingly, analyses to identify possible factors affecting the Th2 polarization secreted from HLA-II-stimulated HGF, prostaglandin E2, was detected only in DQ-sup. The Th2 polarization of nave T cells was blocked in the presence of supernatants from indomethacin-treated HGF with HLA-DQ stimulation. In addition, we found that the culture supernatants of Th cells activated following mixed lymphocyte reaction culture in the presence of DQ-sup had the potential to induce gene expression of type I and III collagens in HGF. These results suggested that fibroblasts stimulated via HLA-DQ molecules promote Th2 polarization in Th-cell responses and showed the counter activation of collagen synthesis, implicating orchestrated responses among these cells in the fibrosis of chronic inflammatory lesions.

Original languageEnglish
Pages (from-to)1747-1756
Number of pages10
JournalLaboratory Investigation
Volume90
Issue number12
DOIs
Publication statusPublished - Dec 2010
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

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    Kato-Kogoe, N., Ohyama, H., Nishimura, F., Meguro, M., Yoshizawa, S., Okada, Y., Nakasho, K., Yamanegi, K., Yamada, N., Hata, M., Higashi, T., Terada, N., & Matsushita, S. (2010). Fibroblasts stimulated via HLA-II molecules produce prostaglandin E 2 and regulate cytokine production from helper T cells. Laboratory Investigation, 90(12), 1747-1756. https://doi.org/10.1038/labinvest.2010.128