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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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Antigen Presentation
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Antigens, CD / metabolism
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Basic-Leucine Zipper Transcription Factors / chemistry
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Basic-Leucine Zipper Transcription Factors / deficiency
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Basic-Leucine Zipper Transcription Factors / genetics
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Basic-Leucine Zipper Transcription Factors / metabolism*
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CD4-Positive T-Lymphocytes / cytology
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CD4-Positive T-Lymphocytes / immunology
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CD8 Antigens / immunology
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CD8 Antigens / metabolism
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CTLA-4 Antigen / metabolism
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Cell Differentiation
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Cell Line, Tumor
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Cell Lineage
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Dendritic Cells / cytology*
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Dendritic Cells / immunology
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Dendritic Cells / metabolism*
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Female
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Fibrosarcoma / immunology
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Fibrosarcoma / metabolism
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Fibrosarcoma / pathology
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Gene Expression Regulation
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Integrin alpha Chains / metabolism
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Interferon Regulatory Factors / deficiency
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Interferon Regulatory Factors / genetics
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Interferon Regulatory Factors / metabolism*
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Interleukin-10 / metabolism
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Interleukin-12 / immunology
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Interleukin-12 / metabolism
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Leucine Zippers
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Male
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Mice
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Mice, Inbred C57BL
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Neoplasm Transplantation
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Oncogene Protein p65(gag-jun) / metabolism
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Protein Binding
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Protein Structure, Tertiary
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Repressor Proteins / deficiency
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Repressor Proteins / genetics
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T-Lymphocytes, Helper-Inducer / cytology
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T-Lymphocytes, Helper-Inducer / immunology
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T-Lymphocytes, Helper-Inducer / metabolism
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Toxoplasma / immunology
Substances
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Antigens, CD
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BATF2 protein, mouse
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Basic-Leucine Zipper Transcription Factors
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Batf protein, mouse
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CD8 Antigens
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CTLA-4 Antigen
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Ctla4 protein, mouse
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Integrin alpha Chains
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Interferon Regulatory Factors
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Oncogene Protein p65(gag-jun)
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Repressor Proteins
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SNFT protein, mouse
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alpha E integrins
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interferon regulatory factor-4
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interferon regulatory factor-8
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Interleukin-10
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Interleukin-12