1. Compensatory dendritic cell development mediated by BATF-IRF interactions.
- Author
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Tussiwand, Roxane, Lee, Wan-Ling, Murphy, Theresa L., Mashayekhi, Mona, KC, Wumesh, Albring, Jörn C., Satpathy, Ansuman T., Rotondo, Jeffrey A., Edelson, Brian T., Kretzer, Nicole M., Wu, Xiaodi, Weiss, Leslie A., Glasmacher, Elke, Li, Peng, Liao, Wei, Behnke, Michael, Lam, Samuel S. K., Aurthur, Cora T., Leonard, Warren J., and Singh, Harinder
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DENDRITIC cells ,INTRACELLULAR pathogens ,T cells ,CYTOKINES ,LEUCINE zippers ,VACCINES - Abstract
The AP1 transcription factor Batf3 is required for homeostatic development of CD8?
+ classical dendritic cells that prime CD8 T-cell responses against intracellular pathogens. Here we identify an alternative, Batf3-independent pathway in mice for CD8?+ dendritic cell development operating during infection with intracellular pathogens and mediated by the cytokines interleukin (IL)-12 and interferon-?. 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. [ABSTRACT FROM AUTHOR]- Published
- 2012
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