Interaction of eosinophils and dermal fibroblasts/keratinocytes in fungal-infection-related atopic dermatitis
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AbstractBackground : Atopic dermatitis (AD) is an allergic disease, histologically characterized by the infiltration of eosinophils to the dermal layer of the skin. This chronic and pruritus disease is often accompanied by the colonization of cutaneous fungal communities such as Malassezia and Candida yeast in the affected skin area. Nevertheless, the interaction between the infiltrating effector cells eosinophils, epidermal keratinocytes (HPEKp), dermal fibroblasts (HDF) and the yeast is not well- understood. Therefore, we aim at investigating the immunological mechanism underlying the fungal interaction with eosinophils in the skin of AD.

Method : Dectin- 1 agonists curdlan and heat- killed Candida albicans (HKCA), as well as the dectin- 2 agonist furfurman, were used to stimulate human eosinophils/primary HDF co- culture or eosinophils/primary HPEKp in 3- dimensional (3D) co- culture. Inflammatory cytokines and adhesion molecules were measured by cytometric bead- based assay and flow cytometry, respectively. H&E staining of the 3D epidermal layers were also performed.

Results : Although dectin- 1 was not expressed on human eosinophils or HDF, the release of AD- related IL- 6, CXCL8, TNF- a and CCL2 in eosinophils/HDF co- culture were significantly upregulated but not in eosinophils single culture upon curdlan stimulation. Adhesion molecule intercellular adhesion molecule (ICAM)- 1 and vascular cell adhesion molecular (VCAM)- 1 were also expressed on HDF. Upon HKCA stimulation, ICAM- 1 and VCAM- 1 on eosinophils were induced. IL- 6 was also exclusively increased in the co- culture system. Dectin- 2, on the other hand, was expressed on both eosinophils and HDF. In eosinophils single culture, the release of TNF- a, IL- 6, CXCL8 and CCL2 were significantly increased by furfurman stimulation. IL- 6 and CXCL8 levels from the co- culture of eosinophils and 3D HPEKp epidermal layers were also increased. H&E staining showed that without direct interaction with eosinophils, there were no structural changes in the 3D epidermal layers upon HKCA or furfurman stimulation.

Conclusion : The increase in pro- inflammatory cytokines and adhesion molecules expression in the eosinophils/HDF co- culture, and in the eosinophils/3D HPEKp cells co- culture system highlight the pathological roles of eosinophils in both dermal and epidermal layers in AD. The results demonstrated the interaction between the skin and eosinophils upon fungal colonization. Further experiments are ongoing to evaluate the underlying pathological mechanism of fungal infection in AD.
All Author(s) ListMiranda Sin-Man Tsang, Tianheng Hou, Xun Gao, Wong Chun Kwok
Name of ConferenceEuropean Academy of Allergy and Clinical Immunology Digital Congress
Start Date of Conference06/06/2020
End Date of Conference08/06/2020
Place of ConferenceLondon - Hybrid
Country/Region of ConferenceGreat Britain
Proceedings TitleAllergy
Volume Number75
Issue NumberSuppl 109
Pages143 - 144
LanguagesEnglish-United Kingdom

Last updated on 2022-15-01 at 00:36