Journal article
Langerhans cells are generated by two distinct PU.1-dependent transcriptional networks
M Chopin, C Seillet, S Chevrier, L Wu, H Wang, HC Morse, GT Belz, SL Nutt
Journal of Experimental Medicine | Published : 2013
DOI: 10.1084/jem.20130930
Abstract
Langerhans cells (LCs) are the unique dendritic cells found in the epidermis. While a great deal of attention has focused on defining the developmental origins of LCs, reports addressing the transcriptional network ruling their differentiation remain sparse. We addressed the function of a group of key DC transcription factors-PU.1, ID2, IRF4, and IRF8-in the establishment of the LC network. We show that although steady-state LC homeostasis depends on PU.1 and ID2, the latter is dispensable for bone marrow-derived LCs. PU.1 controls LC differentiation by regulating the expression of the critical TGF-β responsive transcription factor RUNX3. PU.1 directly binds to the Runx3 regulatory elements ..
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Awarded by National Institute of Allergy and Infectious Diseases
Funding Acknowledgements
This work was supported by project grants (APP1048278 and APP1023266) and fellowships from the National Health and Medical Research Council (NHRMC) of Australia (to L. Wu, G. T. Belz, and S. L. Nutt), and the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases (to H. C. Morse III). S. L. Nutt and G. T. Belz are supported by an Australian Research Council Future Fellowship. This work was made possible through Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIIS.