Mafb lineage tracing to distinguish macrophages from other immune lineages reveals dual identity of Langerhans cells.
Current systems for conditional gene deletion within mouse macrophage lineages are limited by ectopic activity or low efficiency. In this study, we generated a Mafb-driven Cre strain to determine whether any dendritic cells (DCs) identified by Zbtb46-GFP expression originate from a Mafb-expressing population. Lineage tracing distinguished macrophages from classical DCs, neutrophils, and B cells in all organs examined. At steady state, Langerhans cells (LCs) were lineage traced but also expressed Zbtb46-GFP, a phenotype not observed in any other population. After exposure to house dust mite antigen, Zbtb46-negative CD64+inflammatory cells infiltrating the lung were substantially lineage traced, but Zbtb46-positive CD64-cells were not. These results provide new evidence for the unique identity of LCs and challenge the notion that some inflammatory cells are a population of monocyte-derived DCs.
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110.
Xiaodi
0000-0003-0886-8640
X
Wu
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110.
Carlos G
CG
Briseño
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110.
Vivek
V
Durai
Department of Medicine A, Hematology and Oncology, University of Münster, 48149 Münster, Germany.
Jörn C
JC
Albring
Department of Pathology and Laboratory Medicine, Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
Malay
0000-0003-4195-6060
M
Haldar
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110.
Prachi
0000-0001-8886-2577
P
Bagadia
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110.
Ki-Wook
0000-0002-7207-4389
KW
Kim
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110.
Gwendalyn J
0000-0001-9045-1195
GJ
Randolph
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110.
Theresa L
TL
Murphy
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110 kmurphy@wustl.edu.|Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, MO 63110.
Kenneth M
0000-0002-3505-9630
KM
Murphy
D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D019070:Cell Lineage / Q000276:immunology*; D055879:Gene Knock-In Techniques; D018390:Gene Targeting; D006410:Hematopoiesis; D019426:Integrases / Q000378:metabolism; D007801:Langerhans Cells / Q000166:cytology* / Q000378:metabolism*; D008168:Lung / Q000473:pathology; D008264:Macrophages / Q000166:cytology*; D051258:MafB Transcription Factor / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D009000:Monocytes / Q000166:cytology / Q000378:metabolism; D009928:Organ Specificity; D011014:Pneumonia / Q000473:pathology; D014157:Transcription Factors / Q000378:metabolism
D000950:Antigens, Ly; C494192:Ly-6C antigen, mouse; D051258:MafB Transcription Factor; C490406:Mafb protein, mouse; D014157:Transcription Factors; C574226:Zbtb46 protein, mouse; C045073:Cre recombinase; D019426:Integrases