Flt3L dependence helps define an uncharacterized subset of murine cutaneous dendritic cells.

TitleFlt3L dependence helps define an uncharacterized subset of murine cutaneous dendritic cells.
Publication TypeJournal Article
Year of Publication2014
AuthorsMollah SA, Dobrin JS, Feder RE, Tse S-W, Matos IG, Cheong C, Steinman RM, Anandasabapathy N
JournalJ Invest Dermatol
Volume134
Issue5
Pagination1265-75
Date Published2014 May
ISSN1523-1747
KeywordsAdaptive Immunity, Animals, Antigens, CD11b, Antigens, Surface, Cell Movement, Dendritic Cells, Female, Immune Tolerance, Lectins, C-Type, Lymph Nodes, Male, Mannose-Binding Lectins, Membrane Proteins, Mice, Mice, Inbred C57BL, Mice, Knockout, Receptors, CCR7, Receptors, Chemokine, Skin, Transcription Factors
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.

DOI10.1038/jid.2013.515
PubMed URLhttp://www.ncbi.nlm.nih.gov/pubmed/24288007?dopt=Abstract
Alternate JournalJ. Invest. Dermatol.
PubMed ID24288007
PubMed Central IDPMC3994898
Grant List5T32AR007098-39 / AR / NIAMS NIH HHS / United States
AI13013 / AI / NIAID NIH HHS / United States
AI40045 / AI / NIAID NIH HHS / United States
AI81677 / AI / NIAID NIH HHS / United States
AR063461-01A1 / AR / NIAMS NIH HHS / United States
K23 AR063461 / AR / NIAMS NIH HHS / United States
KL2 TR000151 / TR / NCATS NIH HHS / United States
P30 NS072030 / NS / NINDS NIH HHS / United States
R01 AI013013 / AI / NIAID NIH HHS / United States
T32 AR007098 / AR / NIAMS NIH HHS / United States
UL1 TR000043 / TR / NCATS NIH HHS / United States
UL1TR000043/KL2TR000151 / TR / NCATS NIH HHS / United States
/ / Canadian Institutes of Health Research / Canada