GM-CSF-dependent, CD103+ dermal dendritic cells play a critical role in Th effector cell differentiation after subcutaneous immunization.
Dendritic cells (DCs) play an important role in CD4(+) T helper (Th) cell differentiation and in the initiation of both protective and pathogenic immunity. Granulocyte/macrophage colony-stimulating factor (GM-CSF) is a DC growth factor critical for the induction of experimental autoimmune encephalomyelitis (EAE) and other autoimmune diseases, yet its mechanism of action in vivo is not fully defined. We show that GM-CSF is directly required for the accumulation of radiosensitive dermal-derived langerin(+)CD103(+) DCs in the skin and peripheral lymph nodes under steady-state and inflammatory conditions. Langerin(+)CD103(+) DCs stimulated naive myelin-reactive T cells to proliferate and produce IFN-gamma and IL-17. They were superior to other DC subsets in inducing expression of T-bet and promoting Th1 cell differentiation. Ablation of this subset in vivo conferred resistance to EAE. The current report reveals a previously unidentified role for GM-CSF in DC ontogeny and identifies langerin(+)CD103(+) DCs as an important subset in CD4(+) T cell-mediated autoimmune disease.
King
Irah L
IL
Interdepartmental Graduate Program in Neuroscience, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
Kroenke
Mark A
MA
Segal
Benjamin M
BM
D000818:Animals; D015703:Antigens, CD / Q000235:genetics*; D000954:Antigens, Surface / Q000235:genetics*; D001327:Autoimmune Diseases / Q000276:immunology; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D007114:Immunization / Q000379:methods; D039001:Integrin alpha Chains / Q000235:genetics*; D037181:Lectins, C-Type / Q000235:genetics*; D008198:Lymph Nodes / Q000276:immunology; D037241:Mannose-Binding Lectins / Q000235:genetics*; D051379:Mice; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics; D012867:Skin / Q000276:immunology*; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology*; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology*
D015703:Antigens, CD; D000954:Antigens, Surface; C498497:Cd207 protein, mouse; D039001:Integrin alpha Chains; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; C091367:alpha E integrins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor