Increases in Plasmacytoid but Not Myeloid Dendritic Cells (DCs) Parallel the Time Course of Allergen-Induced Cutaneous Late Responses

Abstract

RationaleDCs transport antigens from the periphery to lymphoid tissues and contribute to T cell activation and differentiation. We investigated the numbers and phenotypes of plasmacytoid (pDCs) and myeloid dendritic cells (mDCs) in cutaneous biopsies before and after allergen challenge.Methods3 mm punch skin biopsies were obtained at 8 hr and 48 hr after intradermal allergen (10 biological units in 0.02 ml, ALK Abello, Denmark) and after challenge with allergen diluent from 8 Atopic (AT) and 6 nonatopic subjects (NAC). Dual immunofluorescence microscopy was used to enumerate mDCs (CD1c/BDCA-1) and pDCs (CD303/BDCA-2) and to colocalize DCs to IgE and IFN-α.ResultsIn cutaneous biopsies from AT, pDC numbers were significantly greater at 8 hrs after allergen compared with Dil (p = 0.03). There was also a trend for significance between AT and NAC at 8 hrs (p = 0.08). No changes in mDCs were observed at 8 hr whereas mDCs were markedly increased at 48 hrs compared with Dil (p = 0.02). There was also a trend for significance between AT and NAC at 48 hrs (p = 0.07). Approximately 10% of cutaneous pDCs were IgE-positive after allergen compared to 2% in Dil. In contrast, no allergen-induced changes in IgE-positive mDCs were detected. Similarly, IFN-α expression (a hallmark of pDCs) was elevated on pDCs but not mDCs after challenge.ConclusionsThe peak increase in pDC numbers (but not mDCs) that express FcɛRI and IFN-α coincides with the cutaneous LPR and supports the involvement of pDCs in Th2 cell polarization in man, whereas delayed (48 hr) recruitment of mDCs may possibly be involved in resolution of LPR. RationaleDCs transport antigens from the periphery to lymphoid tissues and contribute to T cell activation and differentiation. We investigated the numbers and phenotypes of plasmacytoid (pDCs) and myeloid dendritic cells (mDCs) in cutaneous biopsies before and after allergen challenge. DCs transport antigens from the periphery to lymphoid tissues and contribute to T cell activation and differentiation. We investigated the numbers and phenotypes of plasmacytoid (pDCs) and myeloid dendritic cells (mDCs) in cutaneous biopsies before and after allergen challenge. Methods3 mm punch skin biopsies were obtained at 8 hr and 48 hr after intradermal allergen (10 biological units in 0.02 ml, ALK Abello, Denmark) and after challenge with allergen diluent from 8 Atopic (AT) and 6 nonatopic subjects (NAC). Dual immunofluorescence microscopy was used to enumerate mDCs (CD1c/BDCA-1) and pDCs (CD303/BDCA-2) and to colocalize DCs to IgE and IFN-α. 3 mm punch skin biopsies were obtained at 8 hr and 48 hr after intradermal allergen (10 biological units in 0.02 ml, ALK Abello, Denmark) and after challenge with allergen diluent from 8 Atopic (AT) and 6 nonatopic subjects (NAC). Dual immunofluorescence microscopy was used to enumerate mDCs (CD1c/BDCA-1) and pDCs (CD303/BDCA-2) and to colocalize DCs to IgE and IFN-α. ResultsIn cutaneous biopsies from AT, pDC numbers were significantly greater at 8 hrs after allergen compared with Dil (p = 0.03). There was also a trend for significance between AT and NAC at 8 hrs (p = 0.08). No changes in mDCs were observed at 8 hr whereas mDCs were markedly increased at 48 hrs compared with Dil (p = 0.02). There was also a trend for significance between AT and NAC at 48 hrs (p = 0.07). Approximately 10% of cutaneous pDCs were IgE-positive after allergen compared to 2% in Dil. In contrast, no allergen-induced changes in IgE-positive mDCs were detected. Similarly, IFN-α expression (a hallmark of pDCs) was elevated on pDCs but not mDCs after challenge. In cutaneous biopsies from AT, pDC numbers were significantly greater at 8 hrs after allergen compared with Dil (p = 0.03). There was also a trend for significance between AT and NAC at 8 hrs (p = 0.08). No changes in mDCs were observed at 8 hr whereas mDCs were markedly increased at 48 hrs compared with Dil (p = 0.02). There was also a trend for significance between AT and NAC at 48 hrs (p = 0.07). Approximately 10% of cutaneous pDCs were IgE-positive after allergen compared to 2% in Dil. In contrast, no allergen-induced changes in IgE-positive mDCs were detected. Similarly, IFN-α expression (a hallmark of pDCs) was elevated on pDCs but not mDCs after challenge. ConclusionsThe peak increase in pDC numbers (but not mDCs) that express FcɛRI and IFN-α coincides with the cutaneous LPR and supports the involvement of pDCs in Th2 cell polarization in man, whereas delayed (48 hr) recruitment of mDCs may possibly be involved in resolution of LPR. The peak increase in pDC numbers (but not mDCs) that express FcɛRI and IFN-α coincides with the cutaneous LPR and supports the involvement of pDCs in Th2 cell polarization in man, whereas delayed (48 hr) recruitment of mDCs may possibly be involved in resolution of LPR.