Mammalian and viral IL-10 enhance C-C chemokine receptor 5 but down-regulate C-C chemokine receptor 7 expression by myeloid dendritic cells: Impact on chemotactic responses and in vivo homing ability

被引:103
作者
Takayama, T
Morelli, AE
Onai, N
Hirao, M
Matsushima, K
Tahara, H
Thomson, AW
机构
[1] Univ Pittsburgh, Med Ctr, Dept Surg, Pittsburgh, PA 15213 USA
[2] Univ Pittsburgh, Thomas E Starzl Transplantat Inst, Pittsburgh, PA 15213 USA
[3] Univ Pittsburgh, Dept Mol Genet & Biochem, Pittsburgh, PA 15213 USA
[4] Univ Tokyo, Sch Med, Dept Mol Prevent Med, Tokyo, Japan
[5] Univ Tokyo, Dept Surg & Bioengn, Inst Med Sci, Tokyo, Japan
关键词
D O I
10.4049/jimmunol.166.12.7136
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The immunosuppressive and anti-inflammatory cytokine IL-10 inhibits the phenotypic and functional maturation of dendritic cells (DC) and has been reported to confer tolerogenic properties on these important professional APC. Here, we exposed murine bone marrow-derived myeloid DC to either mouse (m) or viral (v) IL-10 early during their in vitro generation in response to GM-CSF and IL-4. Both mIL-10 and vIL-10 down-regulated the expression of CCR7 mRNA determined by RT-PCR, while mIL-10 up-regulated the expression of CCR5 transcripts. These changes in CCR7 and CCR5 expression were associated with inhibition and augmentation, respectively, of DC chemotaxis toward their respective agonists, macrophage inflammatory proteins 3 beta and 1 alpha, while in vivo homing of DC from peripheral s.c. sites to secondary lymphoid tissue of syngeneic or allogeneic recipients was significantly impaired. Anti-mIL-10R mAb reversed the effects of mIL-10 on CCR expression and restored DC homing ability. Retroviral transduction of mIL-10- and vIL-10-treated DC to overexpress transgenic CCR7 partially restored the cells' lymphoid tissue homing ability in allogeneic recipients. However, CCR7 gene transfer did not reinstate the capacity of IL-10-treated DC to prime host naive T cells for ex vivo proliferative responses or Th1 cytokine (IFN-gamma) production in response to rechallenge with (donor) alloantigen. These findings suggest that in addition to their capacity to subvert DC maturation/function and confer tolerogenic potential on these cells, mIL-10 and vIL-10 regulate DC migratory responses via modulation of CCR expression.
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收藏
页码:7136 / 7143
页数:8
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