Fibroblasts stimulated via HLA-II molecules produce prostaglandin E₂ and regulate cytokine production from helper T cells.
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 naïve T cells and on the subsequent fibroblast responses. After mixed lymphocyte reaction culture between naïve 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 naïve 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.
Kato-Kogoe
Nahoko
N
Department of Pathology, Hyogo College of Medicine, Nishinomiya, Japan.
Ohyama
Hideki
H
Nishimura
Fusanori
F
Meguro
Michio
M
Yoshizawa
Sayuri
S
Okada
Yuka
Y
Nakasho
Keiji
K
Yamanegi
Koji
K
Yamada
Naoko
N
Hata
Masaki
M
Higashi
Takehiro
T
Terada
Nobuyuki
N
Matsushita
Sho
S
D000328:Adult; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis* / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology; D005347:Fibroblasts / Q000187:drug effects / Q000276:immunology*; D005881:Gingiva / Q000276:immunology; D006683:HLA-DQ Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D018793:Interleukin-13 / Q000276:immunology / Q000378:metabolism; D015848:Interleukin-5 / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D011458:Prostaglandins E / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D016207:Cytokines; D006683:HLA-DQ Antigens; D000949:Histocompatibility Antigens Class II; D018793:Interleukin-13; D015848:Interleukin-5; D011458:Prostaglandins E; D007371:Interferon-gamma