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 CD11blow/−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 CD11blow/−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 CD11blow/−Langerin+ DCs do develop in Csf2rb −/− mice, but that they express reduced, but not absent, levels of CD103. Further, Batf3 −/− mice lacking all peripheral CD11blow/− 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 CD11blow/−Langerin+CD103+ DCs.
Highlights
granulocyte/ macrophage colony stimulating factor (GM-CSF) regulates the development and activity of several myeloid cell types and influences both the initiation and maintenance of adaptive immune responses [1]
We find that Batf32/2 mice develop experimental autoimmune encephalitis (EAE) after immunization and have increased numbers of MOG35–55 peptidespecific T cells, excluding a requirement for either peripheral CD11blow/2CD103+ Dendritic cells (DCs) or lymphoid tissue-resident CD8a+ DCs in EAE development
Batf32/2 mice showed a selective,100-fold reduction in the number of dermal CD11blow/2 Langerin+ DCs. These results indicate that Csf2rb2/2 mice do contain dermal CD11blow/2Langerin+ DCs, but that in the absence of GM-CSF signaling, CD103 expression is reduced
Summary
GM-CSF regulates the development and activity of several myeloid cell types and influences both the initiation and maintenance of adaptive immune responses [1]. Mice lacking GM-CSF or its receptor show decreased antigen specific T cell priming against the encephalitogenic peptide of myelin oligodendrocyte glycoprotein (MOG35–55) and are resistant to EAE [2] Beyond this role in priming adaptive immune responses, GM-CSF acts to sustain ongoing effector responses, both in EAE initiated by MOG35–55 peptide [2] and in collagen-induced arthritis [3]. RORct was shown to induce GM-CSF, which acted on infiltrating myeloid cells entering the CNS, rather than resident microglia, during the development of EAE [7] These studies suggest a model of EAE in which pathogenic T cells secrete GM-CSF that activates myeloid cells infiltrating the CNS to produce pathogenic lesions and further amplifies IL-23 production by DCs [13]
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