Abstract
Nickel (Ni) is the most frequent metal allergen and induces Th1-dependent type-IV allergies. In local skin, epidermal Langerhans cells (LCs) and/or dermal dendritic cells (DCs) uptake antigens and migrate to draining lymph nodes (LNs). However, the subsets of antigen-presenting cells that contribute to Ni presentation have not yet been identified. In this study, we analyzed the Ni-binding capabilities of murine DCs using fluorescent metal indicator Newport Green. Elicitation of Ni allergy was assessed after intradermal (i.d.) injection of Ni-treated DCs into ear pinnae of Ni-sensitized mice. The Ni-binding capabilities of MHC class IIhi CD11cint migratory DCs were significantly stronger than those of MHC class IIint CD11chi resident DCs and CD11cint PDCA1+ MHC class IIint B220+ plasmacytoid DCs. Migratory DCs in skin-draining and mandibular LNs showed significantly stronger Ni-binding capabilities than those in mesenteric and medial iliac LNs. An i.d. injection of IL-1β induced the activation of LCs and dermal DCs with strong Ni-binding capabilities. Ni-binding LCs were detected in draining LNs after i.d. challenge with IL-1β and Ni. Moreover, an i.d. injection of Ni-treated DCs purified from skin-draining LNs elicited Ni-allergic inflammation. These results demonstrated that migratory DCs in skin-draining LNs have strong Ni-binding capabilities and elicit Ni allergy.
Highlights
Nickel (Ni) is the most frequent metal allergen and induces Th1-dependent type-IV allergies
Macrophages, B220+ B cells, CD4+ and CD8+ T cells exhibited significantly weaker Ni-binding capabilities than those of the migratory dendritic cells (DCs) (Fig. 1d and Supplementary Fig. S1). These results indicated that migratory DCs, but not resident DCs or plasmacytoid DCs (pDCs) bound to Ni
Resident DCs in all lymph nodes (LNs) and the spleen exhibited weak Ni-binding capabilities (Fig. 3a,c). These results indicated that migratory DCs in skin-draining and mandibular LNs have strong Ni-binding capabilities
Summary
Nickel (Ni) is the most frequent metal allergen and induces Th1-dependent type-IV allergies. Regulatory T (Treg) cells are induced by various APC subsets including epidermal LCs7, cDC1s in the intestinal mucosa[8], and cDC2s in the sublingual mucosa[9]. These findings indicated that specific APCs are responsible for immune responses against specific Ags. Metal allergies have been classified as type-IV allergies and induce allergic contact dermatitis[10,11]. Bone marrow-derived DCs were shown to be stimulated with Ni through the MAPK pathway[20] These findings indicate that Ni ions stimulate human and murine DCs. the subsets of DCs that respond to Ni have not yet been identified
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