Implication of miR-126 and miR-139-5p in Plasmacytoid Dendritic Cell Dysregulation in Systemic Sclerosis

Eleni Chouri; Maojie Wang; Maarten R Hillen; Chiara Angiolilli; Sandra C Silva-Cardoso; Catharina G K Wichers; Maarten van der Kroef; Cornelis P J Bekker; Marta Cossu; Lenny van Bon; Alsya J Affandi; Tiago Carvalheiro; Aridaman Pandit; Joel A G van Roon; Lorenzo Beretta; Boudewijn M T Burgering; Timothy R D J Radstake; Marzia Rossato

doi:10.3390/jcm10030491

Implication of miR-126 and miR-139-5p in Plasmacytoid Dendritic Cell Dysregulation in Systemic Sclerosis

J Clin Med. 2021 Jan 30;10(3):491. doi: 10.3390/jcm10030491.

Authors

Eleni Chouri^{1

2}, Maojie Wang³, Maarten R Hillen^{1

2}, Chiara Angiolilli^{1

2}, Sandra C Silva-Cardoso^{1

2}, Catharina G K Wichers^{1

2}, Maarten van der Kroef^{1

2}, Cornelis P J Bekker^{1

2}, Marta Cossu^{1

2}, Lenny van Bon^{1

2}, Alsya J Affandi^{1

2}, Tiago Carvalheiro^{1

2}, Aridaman Pandit^{1

2}, Joel A G van Roon^{1

2}, Lorenzo Beretta⁴, Boudewijn M T Burgering³, Timothy R D J Radstake^{1

2}, Marzia Rossato^{1

2

5}

Affiliations

¹ Center of Translational Immunology, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, The Netherlands.
² Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, The Netherlands.
³ Department of Molecular Cancer Research, Center Molecular Medicine, Oncode Institute, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, The Netherlands.
⁴ Scleroderma Unit, Referral Center for Systemic Autoimmune Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano, 20122 Milan, Italy.
⁵ Department of Biotechnology, University of Verona, 37134 Verona, Italy.

Abstract

Compelling evidence shows the involvement of plasmacytoid dendritic cells (pDCs) in systemic sclerosis (SSc) pathogenesis. This study investigated whether microRNAs (miRNAs) are involved in the dysregulation of pDCs in SSc patients already at early stages. RNA from circulating pDCs was isolated from two independent cohorts of SSc patients with different disease phenotypes, and individuals with Raynaud's phenomenon, for microRNA profiling and RNA-sequencing analysis. Proteomic analysis was exploited to identify novel direct miRNA targets at the protein level. Twelve and fifteen miRNAs were differentially expressed in at least one group of patients compared to healthy controls in discovery cohort I and II, respectively. Of note, miR-126 and miR-139-5p were upregulated in both preclinical and definite SSc patients and correlated with the expression of type I interferon (IFN)-responsive genes. Toll-like receptor 9 (TLR9) stimulation of healthy pDCs upregulated the expression of both miRNAs, similarly to what was observed in patients. The proteomic analysis identified USP24 as a novel target of miR-139-5p. The expression level of USP24 was inversely correlated with miR-139-5p expression in SSc patients and induced by TLR9 stimulation in healthy pDCs. These findings demonstrated that the miRNA profile is altered in pDCs of SSc patients already at early stages of the disease and indicate their potential contribution to pDC activation observed in patients.

Keywords: microRNAs (miRNAs); plasmacytoid dendritic cells; systemic sclerosis.

Abstract

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