Prafullakumar B. Tailor
Institute of Science, University of Mumbai, India
Cancer Research Institute, University of Mumbai, India
Section on Molecular Genetics of Immunity,
Laboratory of Molecular Growth Regulation,
National Institute for Child Health and Human Development (NICHD),
National Institutes of Health (NIH), USA.
Dendritic cell Biology, Innate Immunity, Interferon regulatory factors (IRF), Toll likes receptors, Transcription Regulation
Hemant Jaiswal, Rohit Verma, Monika Kaushik, Avinash Londhe, Ajay Bansal.
Summary of Research
Dendritic cells (DCs) are heterogeneous cell populations, comprised of various subsets that collectively provide early innate immunity leading to subsequent adaptive immune responses. Plasmacytoid DCs (pDCs), CD8a+DCs, CD4+DCs and CD8-CD4- DCs are four major DC subsets in mouse spleen and bone marrow cultures. Among DCs, pDCs and CD8a+ DCs produce very high levels of type I Interferon (IFN) and IL12 respectively that help to establish anti-viral anti-microbial states in the body.
Members of Interferon regulatory factors (IRFs) play a critical role in DC development and functions. IRF4 and IRF8 together govern the molecular program regulating DC subset development and functional diversity. IRF8 is essential for pDC and CD8a+ DC development and IRF4 is critical for the development of CD4+ DC subset. IRF8R294C mutation in BXH2 mice abolishes the development of CD8a+ DCs without impairing pDC development and eliminates production of IL12p40, while retaining that of type I IFNs. IRF8R294C mutant would be of immense significance to understand diversity of DC differentiation pathways as change in single amino acid shifts the developmental pathways towards pDCs and CD4+ DCs while blocking CD8a+ DC development. In addition to IRFs, transcription factors such as Relb, Id2 and Batf3 also play critical role in DC subset development. The major pathways and the detailed biochemical mechanisms regulating the DC development and functions remains poorly understood.
Main focus of my lab would be to understand the role of IRFs in DC development and functions. This is relatively new laboratory at NII and there would be lots of fun, hard work and excitement working in my group.
Awards / Fellowships
Ramalingaswami Fellowship from Department of Biotechnology (DBT), Govt. of India.
- Chang T., Xu S., Tailor P., Kanno T., Ozato K. (2012) The Small Ubiquitin-like Modifier-Deconjugating Enzyme Sentrin-Specific Peptidase 1 Switches IFN Regulatory Factor 8 from a Repressor to an Activator during Macrophage Activation. J Immunol. 189: 3548-56.
- Smith M., Wright G., Wu J., Tailor P., Ozato K., Chen X., Wei S., Piskurich J., Ting J., Wright K. (2011) Positive regulatory domain I (PRDM1) and IRF8/PU.1 counter-regulate MHC class II transactivator (CIITA) expression during dendritic cell maturation. J Biol Chem. 286: 7893-904.
- Kwon H, Thierry-Mieg D, Thierry-Mieg J, Kim HP, Oh J, Tunyaplin C, Carotta S, Donovan CE, Goldman ML, Tailor P, Ozato K, Levy DE, Nutt SL, Calame K, Leonard WJ.(2009) Analysis of interleukin-21-induced Prdm1 gene regulation reveals functional cooperation of STAT3 and IRF4 transcription factor. Immunity 3: 941-52.
- Tailor P., Tamura T., Morse H. III, Ozato K. (2008) The BXH2 mutation in IRF8 differentially impairs dendritic cell subset development in the mouse. Blood 111: 1942-1845.
- Tailor, P., Tamura, T., Kong H., Kubota T., Kubota M., Borghi P., Gabrilele, L. and Ozato, K. (2007) Type I interferon induction in dendritic cells requires IRF-8 that effects the feedback phase of transcription. Immunity 27: 228-239.
- Ozato, K., Tailor, P., Kubota T. (2007) The interferon regulatory factor family in host defense: The mechanism of action. J Biol Chem 282: 20065 – 20069.
- Samarasinghe R., Tailor, P., Tamura, T., Kaiso, T., Akira, S., and Ozato, K. Induction of an anti-inflammatory cytokine IL-10 in dendritic cells after Toll-like receptor signaling. J Interferon and Cytokine Research (2006) 26:893-900.
- Tailor, P., Tamura, T., Ozato, K. (2006) IRF family proteins and type I interferon induction in dendritic cells. Cell Research 16: 134-140.
- Tamura, T., Tailor, P., Yamaoka, K., Kong H., Tsujimura H., O’shea, J., Singh H., Ozato, K. (2005) IFN regulatory factor- 4 and -8 govern dendritic cell subset development and their functional diversity. J Immunol 174: 2573-81.
- Cui K., Tailor, P., Liu H., Chen X., Ozato, K., and Zhao, K. (2004) The Chromatin-Remodeling BAF Complex Mediates Cellular Antiviral Activities by Promoter Priming. Molecular and Cellular Biology 24:4476-4486.