Role of Batf2 in Host Defense and CD8α+ Dendritic Cell Development

Date of Award

Winter 12-15-2012

Author's School

Graduate School of Arts and Sciences

Author's Department

Biology & Biomedical Sciences (Immunology)

Degree Name

Doctor of Philosophy (PhD)

Degree Type



Activator protein 1 (AP-1) transcription factors serve important roles in various cellular functions, including cell growth, differentiation and cytokine production. AP-1 transcription factors are composed of homo-dimers or hetero-dimers of Fos, Jun, musculoaponeurotic fibrosarcoma (MAF), and activating transcription factor (ATF) subfamilies of basic leucine-zipper (bZIP) proteins. The basic region is a motif rich in basic amino acid residues and is responsible for DNA binding, while the leucine zipper domain is involved in mediating the dimerization between family members. In cooperation with other transcription factors, AP-1 proteins are shown to directly regulate gene activation. The ATF-like transcription factors Batf and Batf3 were initially suggested to act as repressors of AP-1 transcription due to the lack of transcriptional activation domains (TADs); however, they are now shown to serve unique activities in specific immune cell lineages. Batf deficiency leads to complete blockage in the development of the IL-17-producing T helper cells (TH17) and shows defective development and function of follicular helper T (TFH) cells, as well as impaired class switch recombination (CSR) in B cells, while Batf3 is required for development of CD8α + classical dendritic cells (cDCs) and peripheral CD103+ DCs. In addition, we identified the third ATF-like AP-1 transcription factor, Batf2, which is similar to Batf and Batf3 in its basic region and leucine zipper domain, but has putative TADs in its C-terminus. Batf2 is selectively induced by IFN-gamma and LPS in macrophages and lung CD103+ DCs. Batf2-/- mice displayed significantly decreased survival after infection by Toxoplasma gondii (T. gondii), which was associated with decreased number of pulmonary CD103+ DCs and macrophages following infection. Therefore, Batf2 appeared to play some role in regulating the normal maintenance or expansion of Batf3-dependent CD103+ DCs in the lung following infection with T. gondii. More interestingly, we found Batf2 selectively compensates for the DC defects in Batf3-/- mice, but not for T and B cell defects in Batf-/- mice. Moreover, we recently identify an alternative, cytokine-mediated, Batf3-independent pathway for the development of CD8α + classical dendritic cells during infection. Signals from cytokines IL-12 and IFN-gamma generated in response to pathogens result in molecular compensation for Batf3 by Batf or Batf2. Collectively, these results demonstrate that Batf2 is critical for host resistance to T. gondii infection, and prove a compensatory role for Batf2 in CD8α + cDC development.


English (en)

Chair and Committee

Kenneth M Murphy

Committee Members

Deepta Bhattacharya, Marco Colonna, Brian T Edelson, Takeshi Egawa, Robert D Schreiber


Permanent URL: https://doi.org/10.7936/K7VX0DF3

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