期刊
JOURNAL OF IMMUNOLOGY
卷 174, 期 11, 页码 7154-7159出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.174.11.7154
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资金
- NIAID NIH HHS [AI07532, AI61570, AI53825, AI35914, AI46288] Funding Source: Medline
- NIDDK NIH HHS [DK50306] Funding Source: Medline
- PHS HHS [N0155270] Funding Source: Medline
- Wellcome Trust Funding Source: Medline
A number of receptors and signaling pathways can influence the ability of dendritic cells (DC) to promote CD4(+) Th type 1 (Th1) responses. In contrast, the regulatory pathways and signaling events that govern the ability of DC to instruct Th2 cell differentiation remain poorly defined. In this report, we demonstrate that NF-kappa B1 expression within DC is required to promote optimal Th2 responses following exposure to Schistosoma mansoni eggs, a potent and natural Th2-inducing stimulus. Although injection of S. mansoni eggs induced production of IL-4, IL-5, and IL-13 in the draining lymph node of wild-type (WT) mice, NF-kappa B1(-/-) hosts failed to express Th2 cytokines and developed a polarized Ag-specific IFN-gamma response. In an in vivo adoptive transfer model in which NF-kappa B-sufficient OVA-specific DO11.10 TCR transgenic T cells were injected into OVA-immunized,WT or NF-kappa B1(-/-) busts, NF-kappa B1(-/-) APCs efficiently promoted CD4(+) T cell proliferation and IFN-gamma responses, but failed to promote Ag-specific IL-4 production. Further, bone marrow-derived DC from NF-kappa B1(-/-) mice failed to promote OVA-specific Th2 cell differentiation in in vitro coculture studies. Last, S. mansoni egg Ag-pulsed NF-kappa B1(-/-) DC failed to prime for Th2 cytokine responses following injection into syngeneic WT hosts. Impaired Th2 priming by NF-kappa B1(-/-) DC was accompanied by a reduction in MAPK phosphorylation in Ag-pulsed DC. Taken together, these studies identify a novel requirement for DC-intrinsic expression of NF-kappa B1 in regulating the MAPK pathway and governing the competence of DC to instruct Th2 cell differentiation.
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