Abstract
Dendritic cells (DCs) subsets differ in precursor cell of origin, functional properties, requirements for growth factors, and dependence on transcription factors. Lymphoid-tissue resident CD8α(+) conventional DCs (cDCs) and CD11b(low/-)CD103(+) non-lymphoid DCs are developmentally related, each being dependent on FMS-like tyrosine kinase 3 ligand (Flt3L), and requiring the transcription factors Batf3, Irf8, and Id2 for development. It was recently suggested that granulocyte/macrophage colony stimulating factor (GM-CSF) was required for the development of dermal CD11b(low/-)Langerin(+)CD103(+) DCs, and that this dermal DC subset was required for priming autoreactive T cells in experimental autoimmune encephalitis (EAE). Here, we compared development of peripheral tissue DCs and susceptibility to EAE in GM-CSF receptor deficient (Csf2rb(-/-)) and Batf3(-/-) mice. We find that Batf3-dependent dermal CD11b(low/-)Langerin(+) DCs do develop in Csf2rb(-/-) mice, but that they express reduced, but not absent, levels of CD103. Further, Batf3(-/-) mice lacking all peripheral CD11b(low/-) DCs show robust Th cell priming after subcutaneous immunization and are susceptible to EAE. Our results suggest that defective T effector priming and resistance to EAE exhibited by Csf2rb(-/-) mice does not result from the absence of dermal CD11b(low/-)Langerin(+)CD103(+) DCs.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, CD / metabolism
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Antigens, Surface / metabolism
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Basic-Leucine Zipper Transcription Factors / metabolism*
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CD11b Antigen / metabolism*
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CD8 Antigens / metabolism
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Cross-Priming / drug effects*
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Cytokine Receptor Common beta Subunit / deficiency
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Dendritic Cells / drug effects
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Dendritic Cells / immunology*
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Dermis / immunology
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Dermis / pathology
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Disease Susceptibility
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Encephalomyelitis, Autoimmune, Experimental / immunology
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Encephalomyelitis, Autoimmune, Experimental / pathology
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Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology*
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Immunization*
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Integrin alpha Chains / metabolism
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Lectins, C-Type / metabolism
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Lymph Nodes / drug effects
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Lymph Nodes / immunology
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Mannose-Binding Lectins / metabolism
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Mice
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Mice, Inbred C57BL
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Myelin Proteins / immunology
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Myelin-Oligodendrocyte Glycoprotein
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Repressor Proteins / metabolism*
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Signal Transduction / drug effects
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Spleen / drug effects
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Spleen / immunology
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Subcutaneous Tissue / drug effects
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Subcutaneous Tissue / immunology
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T-Lymphocytes, Helper-Inducer / drug effects
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T-Lymphocytes, Helper-Inducer / immunology*
Substances
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Antigens, CD
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Antigens, Surface
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Basic-Leucine Zipper Transcription Factors
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CD11b Antigen
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CD8 Antigens
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CD8alpha antigen
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Cd207 protein, mouse
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Cytokine Receptor Common beta Subunit
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Integrin alpha Chains
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Lectins, C-Type
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Mannose-Binding Lectins
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Mog protein, mouse
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Myelin Proteins
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Myelin-Oligodendrocyte Glycoprotein
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Repressor Proteins
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SNFT protein, mouse
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alpha E integrins
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Granulocyte-Macrophage Colony-Stimulating Factor