1. Compensatory dendritic cell development mediated by BATF-IRF interactions.
- Author
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Tussiwand R, Lee WL, Murphy TL, Mashayekhi M, KC W, Albring JC, Satpathy AT, Rotondo JA, Edelson BT, Kretzer NM, Wu X, Weiss LA, Glasmacher E, Li P, Liao W, Behnke M, Lam SS, Aurthur CT, Leonard WJ, Singh H, Stallings CL, Sibley LD, Schreiber RD, and Murphy KM
- Subjects
- Animals, Antigen Presentation, Antigens, CD metabolism, Basic-Leucine Zipper Transcription Factors chemistry, Basic-Leucine Zipper Transcription Factors deficiency, Basic-Leucine Zipper Transcription Factors genetics, CD4-Positive T-Lymphocytes cytology, CD4-Positive T-Lymphocytes immunology, CD8 Antigens immunology, CD8 Antigens metabolism, CTLA-4 Antigen metabolism, Cell Differentiation, Cell Line, Tumor, Cell Lineage, Dendritic Cells immunology, Female, Fibrosarcoma immunology, Fibrosarcoma metabolism, Fibrosarcoma pathology, Gene Expression Regulation, Integrin alpha Chains metabolism, Interferon Regulatory Factors deficiency, Interferon Regulatory Factors genetics, Interleukin-10 metabolism, Interleukin-12 immunology, Interleukin-12 metabolism, Leucine Zippers, Male, Mice, Mice, Inbred C57BL, Neoplasm Transplantation, Oncogene Protein p65(gag-jun) metabolism, Protein Binding, Protein Structure, Tertiary, Repressor Proteins deficiency, Repressor Proteins genetics, T-Lymphocytes, Helper-Inducer cytology, T-Lymphocytes, Helper-Inducer immunology, T-Lymphocytes, Helper-Inducer metabolism, Toxoplasma immunology, Basic-Leucine Zipper Transcription Factors metabolism, Dendritic Cells cytology, Dendritic Cells metabolism, Interferon Regulatory Factors metabolism
- Abstract
The AP1 transcription factor Batf3 is required for homeostatic development of CD8α(+) classical dendritic cells that prime CD8 T-cell responses against intracellular pathogens. Here we identify an alternative, Batf3-independent pathway in mice for CD8α(+) dendritic cell development operating during infection with intracellular pathogens and mediated by the cytokines interleukin (IL)-12 and interferon-γ. This alternative pathway results from molecular compensation for Batf3 provided by the related AP1 factors Batf, which also functions in T and B cells, and Batf2 induced by cytokines in response to infection. Reciprocally, physiological compensation between Batf and Batf3 also occurs in T cells for expression of IL-10 and CTLA4. Compensation among BATF factors is based on the shared capacity of their leucine zipper domains to interact with non-AP1 factors such as IRF4 and IRF8 to mediate cooperative gene activation. Conceivably, manipulating this alternative pathway of dendritic cell development could be of value in augmenting immune responses to vaccines.
- Published
- 2012
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