TY - JOUR
T1 - IL-34 is a tissue-restricted ligand of CSF1R required for the development of Langerhans cells and microglia
AU - Wang, Yaming
AU - Szretter, Kristy J.
AU - Vermi, William
AU - Gilfillan, Susan
AU - Rossini, Cristina
AU - Cella, Marina
AU - Barrow, Alexander D.
AU - Diamond, Michael S.
AU - Colonna, Marco
N1 - Funding Information:
stem clones with the targeted allele Il34tm1a(EUCOMM)Wtsi; M. White for injection of Il34tm1a(EUCOMM)Wtsi embryonic stem cells; and T. Doering (Department of Molecular Microbiology, Washington University School of Medicine) for C. albicans strain SC5314. Supported by the National Heart, Lung and Blood Institute (2T32HL007317-31 to Y.W.), Fondazione Beretta (C.R.), Programma di Ricerca di interesse Nazionale of the Ministero dell’Istruzione dell’Università e della Ricerca, 2009 (W.V.), the European Commission Seventh Framework Programme (A.D.B.) and the US National Institutes of Health (GM77279 and HL097805 to M.Co.).
PY - 2012/8
Y1 - 2012/8
N2 - The differentiation of bone marrow-derived progenitor cells into monocytes, tissue macrophages and some dendritic cell (DC) subtypes requires the growth factor CSF1 and its receptor, CSF1R. Langerhans cells (LCs) and microglia develop from embryonic myeloid precursor cells that populate the epidermis and central nervous system (CNS) before birth. Notably, LCs and microglia are present in CSF1-deficient mice but absent from CSF1R-deficient mice. Here we investigated whether an alternative CSF1R ligand, interleukin 34 (IL-34), is responsible for this discrepancy. Through the use of IL-34-deficient (Il34 LacZ/LacZ) reporter mice, we found that keratinocytes and neurons were the main sources of IL-34. Il34 LacZ/LacZ mice selectively lacked LCs and microglia and responded poorly to skin antigens and viral infection of the CNS. Thus, IL-34 specifically directs the differentiation of myeloid cells in the skin epidermis and CNS.
AB - The differentiation of bone marrow-derived progenitor cells into monocytes, tissue macrophages and some dendritic cell (DC) subtypes requires the growth factor CSF1 and its receptor, CSF1R. Langerhans cells (LCs) and microglia develop from embryonic myeloid precursor cells that populate the epidermis and central nervous system (CNS) before birth. Notably, LCs and microglia are present in CSF1-deficient mice but absent from CSF1R-deficient mice. Here we investigated whether an alternative CSF1R ligand, interleukin 34 (IL-34), is responsible for this discrepancy. Through the use of IL-34-deficient (Il34 LacZ/LacZ) reporter mice, we found that keratinocytes and neurons were the main sources of IL-34. Il34 LacZ/LacZ mice selectively lacked LCs and microglia and responded poorly to skin antigens and viral infection of the CNS. Thus, IL-34 specifically directs the differentiation of myeloid cells in the skin epidermis and CNS.
UR - http://www.scopus.com/inward/record.url?scp=84864152036&partnerID=8YFLogxK
U2 - 10.1038/ni.2360
DO - 10.1038/ni.2360
M3 - Article
C2 - 22729249
AN - SCOPUS:84864152036
SN - 1529-2908
VL - 13
SP - 753
EP - 760
JO - Nature immunology
JF - Nature immunology
IS - 8
ER -