1,25-Dihydroxyvitamin D3 Reduces IL-23A and IL-15 mRNA Expression in Autoimmune Polyglandular Syndrome Type 2 (APS-2)

Presentation Number: SUN 332
Date of Presentation: April 2nd, 2017

Anna U Kraus1, Marissa Penna-Martinez2, Gesine Meyer3 and Klaus Badenhoop*3
1University Hospital Frankfurt am Main, Frankfurt/Main, Germany, 2University Hospital, Goethe-University Frankfurt am Main, Germany, 3Goethe-University Hospital, Frankfurt, Germany

Abstract

Introduction: The autoimmune polyglandular syndrome type 2 (APS-2) is a severe endocrinopathy characterized by the co-occurrence of at least two autoimmune mediated diseases of endocrine glands. Interleukin 23 (IL-23) as part of the IL-23/IL-17 immune axis is one of the most crucial cytokines for the induction of autoimmune inflammation. Furthermore, recent data demonstrate the pivotal role of IL-15 overexpression in many organ-specific autoimmune disorders. Thereby pro-inflammatory IL-23 and IL-15 are potential targets for auto-immune therapies. Since the anti-inflammatory and immunomodulatory potential of vitamin D is established, our aim was to investigate the influence of vitamin D stimulation on IL-23 subunit alpha (IL-23A) and IL-15 gene expression in APS-2 patients. Methods: Primary isolated CD14+ monocytes from APS-2 patients (n= 10) and healthy controls (n= 10) were cultured for 24h with or without 1,25-Dihydroxyvitamin D3 (1,25(OH)2D3). For initiating an inflammation IL1β was added to the cultures. After cell culture, gene expression levels of vitamin D receptor (VDR), IL-23A and IL-15 were measured via quantitative real-time-PCR. Transcription levels were analyzed using the comparative cycle threshold (CT) method as means of relative quantification, normalized to endogenous reference 18sRNA and expressed as 2-ΔCTx106. Results: VDR gene expression was significantly reduced by in vitro vitamin D treatment in both APS-2 patients and healthy controls (VDRAPS-2 349 vs. 229, p<0.004; VDRCo 377 vs. 235, p<0.004). Furthermore, gene expression of pro-inflammatory cytokines IL-23A and IL-15 were both inhibited through 1,25(OH)2D3 in APS-2 patients and healthy controls respectively (IL-23AAPS-2  17 vs. 6, p<0.002 and IL-15APS-2 38 vs. 30, p<0.03; IL-23ACo  26 vs. 8, p<0.002 and IL-15Co 26 vs. 21, p<0.03). Conclusion: Vitamin D induces VDR inhibition in APS-2 patients´ monocytes in agreement with previous reports, confirming an intracrine negative feedback mechanism. This indicates a functional impact of vitamin D in APS-2 patients. The gene expression levels of IL-15 were negatively regulated through active vitamin D treatment, suggesting a potential vitamin D-effect on endocrine organ-specific immunity. The significant effect of active vitamin D on IL-23A inhibition infers a positive role in resolving the inflammatory process and autoimmunity mediated by cytokines IL-23/IL-17 .

 

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