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PMID:14499111
| Citation |
Kobayashi, T, Walsh, PT, Walsh, MC, Speirs, KM, Chiffoleau, E, King, CG, Hancock, WW, Caamano, JH, Hunter, CA, Scott, P, Turka, LA and Choi, Y (2003) TRAF6 is a critical factor for dendritic cell maturation and development. Immunity 19:353-63 |
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| Abstract |
IL-1 receptor (IL-1R)/Toll-like receptor (TLR) family and TNF receptor (TNFR) superfamily members are critical for regulating multiple aspects of dendritic cell (DC) biology. Several signaling pathways associated with each family utilize the adapter molecule, TRAF6, but its role in DCs is unclear. By examining TRAF6-deficient mice and bone marrow (BM) chimeras reconstituted with TRAF6-deficient fetal liver cells, we show that proper DC maturation requires TRAF6. In response to either microbial components or CD40L, TRAF6-deficient DCs fail to upregulate surface expression of MHCII and B7.2, or produce inflammatory cytokines. Moreover, LPS-treated TRAF6-deficient DCs do not exhibit an enhanced capacity to stimulate naive T cells. Interestingly, a major population of splenic DCs, the CD4(+)CD8alpha(-) subset, is nearly absent in both TRAF6-deficient mice and BM chimeras. Together these results indicate that TRAF6 regulates the critical processes required for maturation, activation, and development of DCs, the primary cellular bridge between innate and adaptive immunity. |
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| Keywords |
Animals; Antigens, CD4/metabolism; CD40 Ligand/metabolism; Cell Differentiation/genetics; Cell Differentiation/physiology; Dendritic Cells/cytology; Dendritic Cells/metabolism; Mice; Mice, Transgenic; Proteins/genetics; Proteins/metabolism; Proto-Oncogene Proteins/deficiency; Proto-Oncogene Proteins/genetics; Proto-Oncogene Proteins/metabolism; TNF Receptor-Associated Factor 6; Transcription Factor RelB; Transcription Factors/deficiency; Transcription Factors/genetics; Transcription Factors/metabolism |
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Significance
Annotations
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