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2016 ; 148
(1
): 22-33
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Tolerogenic effect of mouse fibroblasts on dendritic cells
#MMPMID26789277
Khosravi-Maharlooei M
; Pakyari M
; Jalili RB
; Salimi-Elizei S
; Lai JC
; Poormasjedi-Meibod M
; Kilani RT
; Dutz J
; Ghahary A
Immunology
2016[May]; 148
(1
): 22-33
PMID26789277
show ga
There is controversy about the immunomodulatory effect of fibroblasts on
dendritic cells (DCs). To clarify this issue, in this study, we have evaluated
different features of fibroblast-primed DCs 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 DCs 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 (CD86) molecules were up-regulated when DCs 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 DCs. Priming of DCs with syngeneic and allogeneic
fibroblasts reduced the proliferation of CD4(+) and CD8(+) T cells. Even
activation of fibroblast- primed DCs failed to restore their ability to induce
T-cell proliferation. Likewise, priming of DCs with fibroblasts blocked the
ability of ovalbumin-pulsed DCs to induce proliferation of ovalbumin-specific
CD4(+) T cells. Compared with non-activated DCs, fibroblast-primed DCs had
significantly higher expression levels of interleukin-10 and indoleamine 2, 3
dioxygenase. Fibroblast-primed DCs had a significantly reduced interleukin-12
expression level compared with that of activated DCs. After priming with
fibroblasts, DCs were able to migrate to lymphatic tissues and present
fibroblast-derived antigens (ovalbumin). In conclusion, after priming with
fibroblasts, DCs gain tolerogenic features. This finding suggests the potential
role of fibroblasts in the maintenance of immune tolerance.
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