Monocytic cytokines in autoimmune polyglandular syndrome type 2 are modulated by vitamin D and HLA-DQ
- Context: Autoimmune polyglandular syndrome (APS-2: autoimmune Addison’s disease or type 1 diabetes) is conferred by predisposing HLA molecules, vitamin D deficiency, and heritable susceptibility. Organ destruction is accompanied by cytokine alterations. We addressed the monocytic cytokines of two distinct APS-2 cohorts, effects of vitamin D and HLA DQ risk. Methods: APS-2 patients (n = 30) and healthy controls (n = 30) were genotyped for HLA DQA1/DQB1 and their CD14+ monocytes stimulated with IL1β and/or 1,25(OH)2D3 for 24 h. Immune regulatory molecules (IL-6, IL-10, IL-23A, IL-15, CCL-2, PD-L1), vitamin D pathway gene transcripts (CYP24A1, CYP27B1, VDR), and CD14 were analyzed by enzyme-linked immunosorbent assay and RTqPCR. Results: Pro-inflammatory CCL-2 was higher in APS-2 patients than in controls (p = 0.001), whereas IL-6 showed a trend – (p = 0.1). In vitro treatment with 1,25(OH)2D3 reduced proinflammatory cytokines (IL-6, CCL-2, IL-23A, IL-15) whereas anti-inflammatory cytokines (IL-10 and PD-L1) rose both in APS-type 1 diabetes and APS-Addison´s disease. Patients with adrenal autoimmunity showed a stronger response to vitamin D. Expression of IL-23A and vitamin D pathway genes VDR and CYP27B1 varied by HLA genotype and was lower in healthy individuals with high-risk HLA (p = 0.0025; p = 0.04), while healthy controls with low-risk HLA showed a stronger IL-10 and CD14 expression (p = 0.01; p = 0.03). Conclusion: 1,25(OH)2D3 regulates the monocytic response in APS-2 disorders type 1 diabetes or Addison´s disease. The monocytic cytokine profile of individuals carrying HLA high-risk alleles is proinflammatory, enhances polyglandular autoimmunity and can be targeted by vitamin D.
Author: | Anna KrausORCiDGND, Marissa Penna Martinez, Firouzeh Shoghi, Gesine MeyerORCiDGND, Klaus BadenhoopORCiDGND |
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URN: | urn:nbn:de:hebis:30:3-575559 |
DOI: | https://doi.org/10.3389/fimmu.2020.583709 |
ISSN: | 1664-3224 |
Parent Title (English): | Frontiers in immunology |
Publisher: | Frontiers Media |
Place of publication: | Lausanne |
Document Type: | Article |
Language: | English |
Date of Publication (online): | 2020/12/07 |
Date of first Publication: | 2020/12/07 |
Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Release Date: | 2020/12/22 |
Tag: | Addison’s disease; HLA DQ haplotypes; autoimmune polyglandular syndrome type 2; autoimmune thyroiditis; cytokine gene expression; type 1 diabetes |
Volume: | 11 |
Issue: | art. 583709 |
Page Number: | 11 |
First Page: | 1 |
Last Page: | 11 |
Note: | This work was supported by the Else Kröner-Fresenius Foundation (EKFS), Research Training Group Translational Research Innovation-Pharma (TRIP) and project funds from the German Diabetes Society (Deutsche Diabetes Gesellschaft-DDG). |
HeBIS-PPN: | 477517285 |
Institutes: | Medizin / Medizin |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Sammlungen: | Universitätspublikationen |
Licence (German): | Creative Commons - Namensnennung 4.0 |