J Exp Med 2013 Dec 16;210(13):2967-80. doi: 10.1084/jem.20130930.
Chopin, M; Seillet, C; Chevrier, S; Wu, L; 3rd Morse, HC; Belz, GT; Nutt, ST
The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.
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 in a TGF-β-dependent manner, whereas ectopic expression of RUNX3 rescued LC differentiation in the absence of PU.1 and promoted LC differentiation from PU.1-sufficient progenitors. These findings highlight the dual molecular network underlying LC differentiation, and show the central role of PU.1 in these processes.
The team at Ozgene has over two decades of experience creating customised knockout and knock-in mice for pivotal medical research globally. Over 300 scientific publications are based on research using Ozgene mice.