Batf3 and Id2 have a synergistic effect on Irf8-directed classical CD8α+ dendritic cell development
Tailor, Prafullakumar B.
KAUST DepartmentImaging and Characterization Core Lab
Advanced Nanofabrication, Imaging and Characterization Core Lab
Permanent link to this recordhttp://hdl.handle.net/10754/563084
MetadataShow full item record
AbstractDendritic cells (DCs) are heterogeneous cell populations represented by different subtypes, each varying in terms of gene expression patterns and specific functions. Recent studies identified transcription factors essential for the development of different DC subtypes, yet molecular mechanisms for the developmental program and functions remain poorly understood. In this study, we developed and characterized a mouse DC progenitor-like cell line, designated DC9, from Irf8-/- bone marrow cells as a model for DC development and function. Expression of Irf8 in DC9 cells led to plasmacytoid DCs and CD8α+ DC-like cells, with a concomitant increase in plasmacytoid DC- and CD8α+ DC-specific gene transcripts and induction of type I IFNs and IL12p40 following TLR ligand stimulation. Irf8 expression in DC9 cells led to an increase in Id2 and Batf3 transcript levels, transcription factors shown to be important for the development of CD8α+ DCs. We show that, without Irf8 , expression of Id2 and Batf3 was not sufficient for directing classical CD8α+ DC development. When coexpressed with Irf8, Batf3 and Id2 had a synergistic effect on classical CD8α+ DC development. We demonstrate that Irf8 is upstream of Batf3 and Id2 in the classical CD8α+ DC developmental program and define the hierarchical relationship of transcription factors important for classical CD8α+ DC development.
SponsorsThis work was supported by the National Institute of Immunology Core Fund. P.T. is a Ramalingaswami fellow, Department of Biotechnology, "Government of India" at National Institute of Immunology. H.J. and R.V. are supported by a fellowship from the Council for Scientific and Industrial Research, Government of India. M.K. is supported by a contingency grant of the Ramalingaswami Fellowship awarded to P.T.
JournalThe Journal of Immunology
- CD8α+ DCs can be induced in the absence of transcription factors Id2, Nfil3, and Batf3.
- Authors: Seillet C, Jackson JT, Markey KA, Brady HJ, Hill GR, Macdonald KP, Nutt SL, Belz GT
- Issue date: 2013 Feb 28
- Batf3 maintains autoactivation of Irf8 for commitment of a CD8α(+) conventional DC clonogenic progenitor.
- Authors: Grajales-Reyes GE, Iwata A, Albring J, Wu X, Tussiwand R, Kc W, Kretzer NM, Briseño CG, Durai V, Bagadia P, Haldar M, Schönheit J, Rosenbauer F, Murphy TL, Murphy KM
- Issue date: 2015 Jul
- NFIL3/E4BP4 is a key transcription factor for CD8α⁺ dendritic cell development.
- Authors: Kashiwada M, Pham NL, Pewe LL, Harty JT, Rothman PB
- Issue date: 2011 Jun 9
- Peripheral CD103+ dendritic cells form a unified subset developmentally related to CD8alpha+ conventional dendritic cells.
- Authors: Edelson BT, KC W, Juang R, Kohyama M, Benoit LA, Klekotka PA, Moon C, Albring JC, Ise W, Michael DG, Bhattacharya D, Stappenbeck TS, Holtzman MJ, Sung SS, Murphy TL, Hildner K, Murphy KM
- Issue date: 2010 Apr 12
- Batf3-independent langerin- CX3CR1- CD8α+ splenic DCs represent a precursor for classical cross-presenting CD8α+ DCs.
- Authors: Petersen TR, Knight DA, Tang CW, Osmond TL, Hermans IF
- Issue date: 2014 Dec