Impaired TH17 responses in patients with chronic mucocutaneous candidiasis with and without autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy

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Impaired TH17 responses in patients with chronic mucocutaneous candidiasis with and without autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy

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Presentation transcript:

Impaired TH17 responses in patients with chronic mucocutaneous candidiasis with and without autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy Wan-Fai Ng, MRCP, PhD, Alexei von Delwig, MD, PhD, Andrew J. Carmichael, MBBS, FRCP, Peter D. Arkwright, MD, PhD, Mario Abinun, MD, PhD, Andrew J. Cant, MD, PhD, Stephen Jolles, MD, PhD, Desa Lilic, MD, PhD Journal of Allergy and Clinical Immunology Volume 126, Issue 5, Pages 1006-1015.e4 (November 2010) DOI: 10.1016/j.jaci.2010.08.027 Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Decreased IL-17 levels in patients with CMC-ht but not in patients with APECED and IL-22 levels in both groups in response to Candida species stimulation. PBMCs (1 × 106 cells/mL) were stimulated with Candida species hyphae, and supernatants were assessed for production of IL-17 (A), IL-22 (B), and IFN-γ (C) by means of ELISA. IL-17 production in response to peptidoglycan (hatched columns) is shown in the inset. Means ± SEMs are shown. Journal of Allergy and Clinical Immunology 2010 126, 1006-1015.e4DOI: (10.1016/j.jaci.2010.08.027) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Patients with CMC-ht but not patients with APECED generate low percentages of IL-17+CD4+ T cells after Candida species stimulation. IFN-γ+CD4+ T cells are decreased in patients with CMC and APECED. Intracellular cytokine staining of Candida species–stimulated PBMCs (1 × 106 cells/mL) is shown as single representative dot plots for each patient group (left panel) and mean percentages or median fluorescence intensity ± SEM (right panel). Journal of Allergy and Clinical Immunology 2010 126, 1006-1015.e4DOI: (10.1016/j.jaci.2010.08.027) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 Patients with CMC-ht have decreased percentages and absolute counts of IL-17+CD4+ but not CD4+IFN-γ+ cells proliferating to Candida species. PBMCs were stained with CFSE and stimulated with Candida species, followed by flow cytometric assessment of intracellular cytokine staining and proliferation (CFSElo cells). Data represent percentages and absolute counts of CD4+IL-17+ (A and B) and CD4+IFN-γ+ cells (C and D). NS, Not significant. Journal of Allergy and Clinical Immunology 2010 126, 1006-1015.e4DOI: (10.1016/j.jaci.2010.08.027) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 Plasma from patients with APECED abrogates IL-17 but not IFN-γ production by autologous Candida species–stimulated PBMCs. PBMCs (1 × 106 cells/mL) from 3 patients with APECED were stimulated with Candida species hyphae and cultured in 5% autologous or control plasma. APECED plasma completely abrogated IL-17 production (A-C), whereas IFN-γ production was unaffected by APECED plasma (D and E). Journal of Allergy and Clinical Immunology 2010 126, 1006-1015.e4DOI: (10.1016/j.jaci.2010.08.027) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 5 APECED plasma but not control plasma inhibits Candida species–induced proliferation of CD4+IL-17+ T cells. Control PBMCs (1 × 106 cells/mL) were stained with CFSE before cultivation in 5% plasma from 2 patients with APECED or a healthy control subject. APECED plasma significantly inhibited proliferation of CD4+IL-17+ (A and B) but not CD4+IFN-γ+ (C and D) cells. Journal of Allergy and Clinical Immunology 2010 126, 1006-1015.e4DOI: (10.1016/j.jaci.2010.08.027) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 6 Both patients with CMC-ht and patients with APECED produce normal levels of IL-6 and IL-23 on stimulation with Candida species. PBMCs (1 × 106 cells/mL) from healthy control subjects, patients with CMC-ht, and patients with APECED were left unstimulated or stimulated with Candida species hyphae or LPS for 1 day. Production of IL-6 (upper panel) and IL-23 (lower panel) in supernatants was measured by means of ELISA. Means ± SEMs are shown. Journal of Allergy and Clinical Immunology 2010 126, 1006-1015.e4DOI: (10.1016/j.jaci.2010.08.027) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Patients with CMC-ht but not patients with CMC-APECED generate low percentages of IL-17+CCR6/CCR4+CD4+ T cells after Candida species stimulation. IFN-γ+CCR6/CXCR3+CD4+ T cells are comparable in all groups. PBMCs (1 × 106 cells/mL) were stimulated with Candida species, followed by flow cytometric assessment of intracellular cytokine staining. Mean percentages ± SEMs of IL-17+CCR6/CCR4+CD4+ lymphocytes (A) and IFN-γ+CCR6/CXCR3+CD4+ lymphocytes (B) are presented. Journal of Allergy and Clinical Immunology 2010 126, 1006-1015.e4DOI: (10.1016/j.jaci.2010.08.027) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Plasma from patients with APECED abrogates IL-17 but not IFN-γ production by control Candida species–stimulated PBMCs. PBMCs (1 × 106 cells/mL) from 2 healthy control subjects were stimulated with Candida species hyphae and cultured in 5% APECED or control plasma. APECED plasma completely abrogated IL-17 production (A and B), whereas IFN-γ production was unaffected by APECED plasma (C and D). Journal of Allergy and Clinical Immunology 2010 126, 1006-1015.e4DOI: (10.1016/j.jaci.2010.08.027) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions