Research

Prafullakumar B. Tailor

M. Sc.
Institute of Science, University of Mumbai, India

Ph. D.
Cancer Research Institute, University of Mumbai, India

Postdoctoral Research
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.

Email
tailorp@nii.ac.in

 

Research Interest

Dendritic cell Biology, Innate Immunity, Interferon regulatory factors (IRF), Toll like receptors (TLRs), Transcription Regulation of DC differentiation, Applied Immunology. 

Group Members

Kuldeep Singh Chauhan, Bhupendra Singh Rawat, Annesa Das, Ramya Venkataraman, Yadhu Sharma, 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), CD8α+ DCs, CD4+ DCs and CD8-CD4- DCs are four major DC subsets in mouse spleen and bone marrow cultures. Among DCs, pDCs and CD8α+ 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. In a simplified system of DC classification, CD8α+ DC and equivalent population from various tissues is classified as cDC1 whereas CD4+ DC equivalent population is classified as cDC2 subtype.

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. Studies from knockout mouse model led to identification of critical role for Inhibitor of DNA binding 2 (Id2), Basic leucine zipper transcription factor 3 (Batf3) in development of CD8α+ DC. We reported that Irf8 is upstream of Batf3 and Id2 in the classical CD8α+ DC developmental program and demonstrated that Batf3 and Id2 had a synergistic effect on Irf8 directed developmental process (J. Immunol. 2013, 191:5993-6001).

Analyzing of the effect of Irf8 on TGF-β super family specific gene expression in DCs in lab led to identification of Acvrl1, a type I TGF-β superfamily receptor, as a gene strongly induced by Irf8 expression. We showed that among various DC subtypes, Acvrl1 is differentially expressed in CD8α+ DCs. ACVRL1 signaling augmented Irf8-directed classical CD8α+ DC development. IRF8R294C mutation in BXH2 mice abolishes the development of CD8α+ DCs without impairing pDC development and eliminates production of IL12p40, while retaining that of type I IFNs. IRF8R294C mutant failed to induce ACVRL1 transcription which co-related with defect in development of CD8α+ DCs in BXH2 mice. Irf8 expression is essential for plasmacytoid DC and CD8α+ DC development and ACVRL1 signaling plays a pivotal role whereby it suppresses plasmacytoid DC development while enhancing that of CD8α+ DCs, thus contributing to DC diversity 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 biology and examining role of DC subsets in various pathological conditions.

Awards / Fellowships

Ramalingaswami Fellowship from Department of Biotechnology (DBT), Govt. of India.
Mid-career scientist Award from Indian immunology Society (IIS).

Selected Publications

  • Mishra R, Bhattacharya S, Singh Rawat B, Kumar A, Kumar A, Niraj K, Chande A, Gandhi P, Khetan D, Aggarwal A, Sato S, Tailor P, Takaoka, A, Kumar H (2020) MicroRNA-30e-5p has an Integrated Role in the Regulation of the Innate Immune Response during Virus Infection and Systemic Lupus Erythematosus. iScience, 23(7):101322.
  • Saha I, Jaiswal H, Mishra R, Nel HJ, Schreuder J, Kaushik M, Singh Chauhan K, Singh Rawat B, Thomas R, Naik S, Kumar H, Tailor P (2020) RelB suppresses type I Interferon signaling in dendritic cells. Cellular Immunology, 304: 104043.
  • Kumari P, Saha I, Narayanan A, Narayanan S, Takaoka A, Senthil Kumar N, Tailor P and Kumar H (2017) Essential role of HCMV deubiquitinase in promoting oncogenesis by targeting anti-viral innate immune signaling pathways. Cell Death and Disease, 8;e3078.
  • Verma R, Jaiswal H, Chauhan KS, Kaushik M and Tailor P (2016) ACVRL1 signaling  augments CD8α+dendritic cell development. Cuttting Edge section: J Immunol 197: 1129-1134.
  • Jaiswal H, Kaushik M, Sougrat R, Gupta M, Dey A, Verma R, Ozato K and Tailor P (2013) Batf3 and Id2 have a synergistic effect on Irf8-Directed classical CD8α+ dendritic cell development. J Immunol 191: 5993-6001.
  • Goel P, Tailor P, Chande AG Basu A., Mukhopadhyaya R (2013) An infectious HHV-6B isolate from a healthy adult with chromosomally integrated virus and a reporter based relative viral titer assay. Virus Research 173: 280-285.
  • 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.

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