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Tolerogenic effect of mouse fibroblasts on dendritic cells
Author(s) -
KhosraviMaharlooei Mohsen,
Pakyari MohammadReza,
Jalili Reza B.,
SalimiElizei Sanam,
Lai Jacqueline C. Y.,
PoormasjediMeibod Malihesadat,
Kilani Ruhangiz T.,
Dutz Jan,
Ghahary Aziz
Publication year - 2016
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12584
Subject(s) - fibroblast , dendritic cell , follicular dendritic cells , priming (agriculture) , ovalbumin , microbiology and biotechnology , cd8 , cd86 , immunology , t cell , antigen presentation , immune system , biology , chemistry , antigen presenting cell , in vitro , biochemistry , botany , germination
Summary There is controversy about the immunomodulatory effect of fibroblasts on dendritic cells ( DC s). To clarify this issue, in this study, we have evaluated different features of fibroblast‐primed DC s including their ability to express co‐inhibitory and co‐stimulatory molecules, pro‐inflammatory and anti‐inflammatory cytokines and their ability to induce T‐cell proliferation. We also examined migratory capacity of DC s to lymphatic tissues and present fibroblast‐derived antigens after encountering fibroblasts. The results of our in vitro study showed that both co‐inhibitory (programmed death ligand 1 and ligand 2 and B7H4) and co‐stimulatory ( CD 86) molecules were up‐regulated when DC s were co‐cultured with fibroblasts. In an animal model, we showed that intra‐ peritoneal injection ( IP ) of both syngeneic and allogeneic fibroblasts significantly increased both total DC count and expression level of co‐inhibitory and co‐stimulatory molecules on DC s. Priming of DC s with syngeneic and allogeneic fibroblasts reduced the proliferation of CD 4 + and CD 8 + T cells. Even activation of fibroblast‐ primed DC s failed to restore their ability to induce T‐cell proliferation. Likewise, priming of DC s with fibroblasts blocked the ability of ovalbumin‐pulsed DC s to induce proliferation of ovalbumin‐specific CD 4 + T cells. Compared with non‐activated DC s, fibroblast‐primed DC s had significantly higher expression levels of interleukin‐10 and indoleamine 2, 3 dioxygenase. Fibroblast‐primed DC s had a significantly reduced interleukin‐12 expression level compared with that of activated DC s. After priming with fibroblasts, DC s were able to migrate to lymphatic tissues and present fibroblast‐derived antigens (ovalbumin). In conclusion, after priming with fibroblasts, DC s gain tolerogenic features. This finding suggests the potential role of fibroblasts in the maintenance of immune tolerance.

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