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4 th International Conference and Exhibition on Immunology

4 th International Conference and Exhibition on Immunology. Batf is essential for IL-4 expression in T follicular helper cells. Roza Nurieva. Center for Cancer Immunology Research, MD Anderson Cancer Center. Houston, TX. USA. 4 th International Conference and Exhibition on Immunology.

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4 th International Conference and Exhibition on Immunology

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  1. 4th International Conference and Exhibition on Immunology Batf is essential for IL-4 expression in T follicular helper cells. RozaNurieva Center for Cancer Immunology Research, MD Anderson Cancer Center. Houston, TX. USA

  2. 4th International Conference and Exhibition on Immunology T helper subsets: differentiation and function BMC Biology, 2010

  3. 4th International Conference and Exhibition on Immunology Transcriptional control of T helper subsets IL-4 TH2 Tfh IL-4 Roza Nurieva Tfh

  4. 4th International Conference and Exhibition on Immunology Il-4 transcription in Th2 and Tfh cells • In Th2 cells: Various Cis-Regulatory Elements including Il4 Promoter and TFS GATA3 Blood, 2010 • In Tfh cells: CNS2 element of the IL-4 locus and TFs? • The 3′ enhancer CNS2 is a critical regulator of interleukin-4-mediated humoral immunity in follicular helper T cells. Immunity, 2012.

  5. 4th International Conference and Exhibition on Immunology Basic leucine zipper transcription factor, ATF-like(BATF) • Batf belongs to the AP-1/ATF superfamily of transcription factors and is thought to be a negative regulator of AP-1/ATF transcriptional events. • The AP-1 transcription factor Batf controls TH17 differentiation. Nature,2009 • Batf coordinates multiple aspects of B and T cell function required for normal antibody responses. Journal of experimental medicine,2010. • Nature immunology, 2011. Nature Immunology, 2011

  6. 4th International Conference and Exhibition on Immunology Batf is expressed in Th2 and Tfh cells A. B. • CD4+CD44hiCXCR5hiPD1hi (Tfh) • CD4+CD44hiCXCR5- (nTfh) • Active histone modifications (AcH3,H3k4)

  7. 4th International Conference and Exhibition on Immunology Batf deficiency abrogates Th2 cytokines in vivo • WT and Batf deficient mice immunized with ovalbumin in alum.

  8. 4th International Conference and Exhibition on Immunology Batf has partial control over Th2 genes in vitro A. B. C. *

  9. 4th International Conference and Exhibition on Immunology The IL-4 defect in Tfh cells upon Batf deficiency is T cell intrinsic

  10. 4th International Conference and Exhibition on Immunology IL-4 producing Tfh cells can trigger asthmatic symptoms WT and Batf KO mice (CD45.2+) B6SJL mice (CD45.1+) Intra nasal ova for 3 days Asthma iv transfer Sort Tfh cells Analysis 2X10^5 cells A. B. C.

  11. 4th International Conference and Exhibition on Immunology Il-4 transcription in Th2 and Tfh cells • In Th2 cells: Cis-Regulatory Elements including Il4 Promoter GATA3 Blood, 2010 • In Tfh cells: CNS2 element of the IL-4 locus and TFs? • The 3′ enhancer CNS2 is a critical regulator of interleukin-4-mediated humoral immunity in follicular helper T cells. Immunity, 2012.

  12. 4th International Conference and Exhibition on Immunology Batf in cooperation with IRF4 regulates IL-4 expression in Tfh cells through the CNS2 locus

  13. 4th International Conference and Exhibition on Immunology Batf/IRF4 along with Stat3 and Stat6 controls IL-4 production in Tfh cells

  14. 4th International Conference and Exhibition on Immunology Summary • The transcription factor Batf, a member of the AP-1/Jun family, shows enhanced expression in both Th2 and Tfh cells. • Functionally, Batf is required for IL-4 expression in Tfh cells and its deficiency leads to subsequent reduction in their pro-allergic function. • Batf in cooperation with IRF4 and along with Stat3 and Stat6 controls IL-4 production in Tfh cells by directly binding to and activation of the CNS2 region of the IL-4 locus. These results indicate a critical role of Batf in promoting the generation of pro-allergic IL-4 producing Tfh cells.

  15. 4th International Conference and Exhibition on Immunology Acknowledgement Roza Nurieva Dr. Chen Dong Kentaro Tanaka Anupama Sahoo Andrei Alekseev Lydia Obertas Beatrisa Lerman Divyendu Singh Shradha Wali Sushant Puri MD Anderson FACS Core facility

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