TRAF6 Is a Critical Factor for Dendritic Cell Maturation and Development

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. B...

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Bibliographic Details
Published in:Immunity (Cambridge, Mass.) Mass.), 2003-09, Vol.19 (3), p.353-363
Main Authors: Kobayashi, Takashi, Walsh, Patrick T, Walsh, Matthew C, Speirs, Kendra M, Chiffoleau, Elise, King, Carolyn G, Hancock, Wayne W, Caamano, Jorge H, Hunter, Christopher A, Scott, Phillip, Turka, Laurence A, Choi, Yongwon
Format: Article
Language:English
Subjects:
Animals
CD4 Antigens - metabolism
CD40 Ligand - metabolism
CD40L protein
Cell Differentiation - genetics
Cell Differentiation - physiology
Cytokines
Dendritic Cells - cytology
Dendritic Cells - metabolism
Deoxyribonucleic acid
DNA
Immune system
interleukin 1 receptors
Kinases
Lymphocytes
Mice
Mice, Transgenic
Proteins - genetics
Proteins - metabolism
Proto-Oncogene Proteins - deficiency
Proto-Oncogene Proteins - genetics
Proto-Oncogene Proteins - metabolism
T cell receptors
TNF Receptor-Associated Factor 6
TRAF6 protein
Transcription Factor RelB
Transcription factors
Transcription Factors - deficiency
Transcription Factors - genetics
Transcription Factors - metabolism
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Summary: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 +CD8α − 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.
ISSN:1074-7613
1097-4180
DOI:10.1016/S1074-7613(03)00230-9