期刊
CLINICAL AND EXPERIMENTAL ALLERGY
卷 46, 期 12, 页码 1564-1574出版社
WILEY
DOI: 10.1111/cea.12787
关键词
Aspergillus fumigatus; Candida albicans; chronic mucocutaneous candidiasis; fungal allergy; hyper-IgE syndrome; interleukin-13; interleukin-5; interleukin-9; Staphylococcus aureus; Th2 response
资金
- Netherlands Organization for Scientific Research
- Radboudumc
- ERC [310372]
- ERA-Net for Research Programmes on Rare Diseases (EURO-CMC)
Background STAT1 mutations cause chronic mucocutaneous candidiasis (CMC), while STAT3 mutations cause hyper-IgE syndrome (HIES). CMC and HIES patients have T helper (Th) 17 defects suffering from mucosal Candida infections, but only patients with HIES show an allergic phenotype with eczema, eosinophilia and high IgE levels. Objective We investigated whether differential Th2 and Th9 responses may explain the clinical differences. Methods Peripheral blood mononuclear cells of patients with CMC (n = 4), patients with HIES (n = 4), patients with atopic dermatitis (n = 4) and healthy volunteers (n = 13) were stimulated with Candida and Staphylococcus aureus, with and without IL-4. The cytokines IL-5, IL-13, IL-9, IL-17 and TGFb and regulatory T cells were measured in cell culture supernatants by ELISA or flow cytometry, respectively. Results Peripheral blood mononuclear cells of patients with CMC showed a significantly impaired production of the Th2 cytokines IL-5 and IL-13, especially in the presence of IL4. Moreover, IL-9 production was significantly lower in patients with CMC compared to healthy controls. In contrast, patients with HIES and patients with AD showed normal IL5 and IL-13 production, while IL-9 production was significantly lower in patients with HIES compared to healthy controls. Although TGFb was involved in the IL-4-induced IL-9 production, TGFb levels and the frequency of regulatory T cells did not differ between patients with HIES and controls. Flow cytometry analysis demonstrated an IL-9 + IL17 + CD4 + subset in healthy controls after stimulation with Candida which was less present in patients with HIES. Conclusion Patients with CMC have a general Th defect including Th2 and Th9, while patients with HIES have normal Th2 cytokines. These differences are in line with their clinical presentation. Surprisingly, the allergic cytokine IL-9 was deficient in both HIES and CMC, suggesting a Th-17-derived origin.
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