title: Batf3-dependent CD11b(low/-) peripheral dendritic cells are GM-CSF-independent and are not required for Th cell priming after subcutaneous immunization.
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.
authors: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, United States of America.
authors: Brian T
authors: BT
authors: Edelson
authors: Tara R
authors: TR
authors: Bradstreet
authors: Wumesh
authors: W
authors: KC
authors: Kai
authors: K
authors: Hildner
authors: Jeremy W
authors: JW
authors: Herzog
authors: Julia
authors: J
authors: Sim
authors: John H
authors: JH
authors: Russell
authors: Theresa L
authors: TL
authors: Murphy
authors: Emil R
authors: ER
authors: Unanue
authors: Kenneth M
authors: KM
authors: Murphy
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000954:Antigens, Surface / Q000378:metabolism; D050976:Basic-Leucine Zipper Transcription Factors / Q000378:metabolism*; D039481:CD11b Antigen / Q000378:metabolism*; D016827:CD8 Antigens / Q000378:metabolism; D045142:Cross-Priming / Q000187:drug effects*; D053648:Cytokine Receptor Common beta Subunit / Q000172:deficiency; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D020405:Dermis / Q000276:immunology / Q000473:pathology; D004198:Disease Susceptibility; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000473:pathology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D007114:Immunization; D039001:Integrin alpha Chains / Q000378:metabolism; D037181:Lectins, C-Type / Q000378:metabolism; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology; D037241:Mannose-Binding Lectins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009185:Myelin Proteins / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D012097:Repressor Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D040521:Subcutaneous Tissue / Q000187:drug effects / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D000954:Antigens, Surface; D050976:Basic-Leucine Zipper Transcription Factors; D039481:CD11b Antigen; D016827:CD8 Antigens; C431698:CD8alpha antigen; C498497:Cd207 protein, mouse; D053648:Cytokine Receptor Common beta Subunit; D039001:Integrin alpha Chains; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins; C571327:Mog protein, mouse; D009185:Myelin Proteins; D063308:Myelin-Oligodendrocyte Glycoprotein; D012097:Repressor Proteins; C533289:SNFT protein, mouse; C091367:alpha E integrins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor