Mast cells generated from patients with atopic eczema have enhanced levels of granule mediators and an impaired Dectin-1 expression.
BACKGROUND
The disrupted skin barrier of patients with atopic eczema (AE) might facilitate contact between mast cells (MCs) in the skin and environmental triggers of the disease. One such trigger is the skin-colonizing yeast Malassezia sympodialis (M. sympodialis). In this study, we investigated the interaction of MC with M. sympodialis.


METHODS
Mast cells were generated from peripheral blood CD34(+) progenitor cells of healthy controls (HC) and M. sympodialis-sensitized AE patients. Biopsy specimens were taken from HC and lesional AE skin for immunohistological stainings.


RESULTS
The progenitor-derived MCs expressed the macrophage-inducible C-type lectin receptor Mincle, and exposure of these cells to M. sympodialis induced up-regulation of the mRNA expression of Mincle. Furthermore, we demonstrate that, when compared to HC, the progenitor-derived MCs from AE patients (i) contain more intrinsic granule mediators such as histamine, (ii) exhibit enhanced IL-6 release in response to M. sympodialis exposure, and (iii) have an impaired up-regulation of the fungal recognition receptor Dectin-1. In addition, analysis of skin sections from HC and AE patients revealed MCs as the predominant Dectin-1-expressing cell type in the skin.


CONCLUSIONS
Our data indicate that progenitor-derived MCs from AE patients differ from those from HC. Further investigations with skin-derived MCs are necessary to confirm the observed differences which could provide new insights into the pathogenic mechanisms underlying AE.
Ribbing
C
C
Department of Medicine Solna Clinical Allergy Research Unit, Karolinska Institutet and University Hospital Solna, Stockholm, Sweden.
Engblom
C
C
Lappalainen
J
J
Lindstedt
K
K
Kovanen
P T
PT
Karlsson
M A
MA
Lundeberg
L
L
Johansson
C
C
Nilsson
G
G
Lunderius-Andersson
C
C
Scheynius
A
A
D000328:Adult; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology*; D003881:Dermatomycoses / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D006632:Histamine / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D037181:Lectins, C-Type / Q000378:metabolism; D008290:Malassezia / Q000276:immunology / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000166:cytology / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D012867:Skin / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D053802:Tryptases / Q000378:metabolism*; D015854:Up-Regulation; D055815:Young Adult; D000099181:Dectin-1
D016207:Cytokines; D006632:Histamine; D015850:Interleukin-6; D037181:Lectins, C-Type; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D053802:Tryptases; D000099181:Dectin-1