title: Flt3L dependence helps define an uncharacterized subset of murine cutaneous dendritic cells.
abstract: Skin-derived dendritic cells (DCs) are potent antigen-presenting cells with critical roles in both adaptive immunity and tolerance to self. Skin DCs carry antigens and constitutively migrate to the skin-draining lymph nodes (LNs). In mice, Langerin-CD11b- dermal DCs are a low-frequency, heterogeneous, migratory DC subset that traffics to LNs (Langerin-CD11b- migDCs). Here, we build on the observation that Langerin-CD11b- migDCs are Fms-like tyrosine kinase 3 ligand (Flt3L) dependent and strongly Flt3L responsive, which may relate them to classical DCs. Examination of DC capture of FITC from painted skin, DC isolation from skin explant culture, and from the skin of CCR7 knockout mice, which accumulate migDCs, demonstrate these cells are cutaneous residents. Langerin-CD11b- Flt3L-responsive DCs are largely CD24(+) and CX3CR1(low) and can be depleted from Zbtb46-DTR mice, suggesting classical DC lineage. Langerin-CD11b- migDCs present antigen with equal efficiency to other DC subsets ex vivo, including classical CD8α cDCs and Langerin+CD103+ dermal DCs. Finally, transcriptome analysis suggests a close relationship with other skin DCs, and a lineage relationship with other classical DCs. This work demonstrates that Langerin- CD11b- dermal DCs, a previously overlooked cell subset, may be an important contributor to the cutaneous immune environment.
authors.affiliation: Hospital Informatics, Rockefeller University, New York, New York, USA.
authors.forename: Shamim A
authors.initials: SA
authors.lastname: Mollah
authors.affiliation: Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, New York, USA; Christopher H. Browne Center for Immunology and Immune Diseases Rockefeller University, New York, New York, USA.
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Dobrin
authors.affiliation: Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, New York, USA; Christopher H. Browne Center for Immunology and Immune Diseases Rockefeller University, New York, New York, USA.
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Feder
authors.affiliation: Laboratory of Cellular Physiology and Immunology, Institut de Recherches Cliniques de Montréal (IRCM), Montréal, Canada.
authors.forename: Sze-Wah
authors.initials: SW
authors.lastname: Tse
authors.affiliation: Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, New York, USA; Christopher H. Browne Center for Immunology and Immune Diseases Rockefeller University, New York, New York, USA.
authors.forename: Ines G
authors.initials: IG
authors.lastname: Matos
authors.affiliation: Laboratory of Cellular Physiology and Immunology, Institut de Recherches Cliniques de Montréal (IRCM), Montréal, Canada.
authors.forename: Cheolho
authors.initials: C
authors.lastname: Cheong
authors.affiliation: Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, New York, USA; Christopher H. Browne Center for Immunology and Immune Diseases Rockefeller University, New York, New York, USA.
authors.forename: Ralph M
authors.initials: RM
authors.lastname: Steinman
authors.affiliation: Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, New York, USA; Christopher H. Browne Center for Immunology and Immune Diseases Rockefeller University, New York, New York, USA; Department of Dermatology/Harvard Skin Disease Research Center, Brigham and Women's Hospital, Harvard Institute of Medicine, Boston, Massachusetts, USA. Electronic address: nanandasabapathy@partners.org.
authors.forename: Niroshana
authors.initials: N
authors.lastname: Anandasabapathy
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology; D000818:Animals; D000954:Antigens, Surface / Q000276:immunology / Q000378:metabolism; D039481:CD11b Antigen / Q000276:immunology / Q000378:metabolism; D000073883:CX3C Chemokine Receptor 1; D002465:Cell Movement / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology*; D005260:Female; D007108:Immune Tolerance / Q000276:immunology; D037181:Lectins, C-Type / Q000276:immunology / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008297:Male; D037241:Mannose-Binding Lectins / Q000276:immunology / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054400:Receptors, CCR7 / Q000235:genetics; D019707:Receptors, Chemokine / Q000235:genetics; D012867:Skin / Q000166:cytology* / Q000276:immunology*; D014157:Transcription Factors / Q000276:immunology / Q000378:metabolism
chemical_list: D000954:Antigens, Surface; D039481:CD11b Antigen; D000073883:CX3C Chemokine Receptor 1; C515371:Ccr7 protein, mouse; C498497:Cd207 protein, mouse; C471885:Cx3cr1 protein, mouse; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins; D008565:Membrane Proteins; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D014157:Transcription Factors; C574226:Zbtb46 protein, mouse; C084881:flt3 ligand protein