TH17 cells\xa0expressing CD146 are significantly increased in patients with Systemic sclerosis

Amira Gabsi,Akram Dlala,Marcel Blot-Chabaud,Alexandrine Bertaud,Bilel Neili,Aurelie S Leroyer,Ahmed Abidi,Monia Smiti Khanfir,Brigitte Granel,Raja Marrakchi,Mohamed Habib Houman,Nathalie Bardin,Xavier Heim,Asma Gati,Sonia Amri,Fatma Said,Haifa Sakhri

doi:10.1038/s41598-019-54132-y

Abstract

Systemic sclerosis (SSc) is an autoimmune disorder characterized by vascular damage, excessive fibrosis and abnormal T cells immune-regulation. CD146 is an adhesion molecule essentially expressed in the vascular system, but also on TH17 lymphocytes. In view of the recently described role of CD146 in SSc, we hypothesized an involvement of CD146 positive TH17 cells in this disease. Compared to healthy controls, we showed that both soluble form of CD146 (sCD146), and IL17A levels were increased in patients with SSc with a positive correlation between both factors. A significant increase in TH17 cells attested by an increase of RORγT, IL17A mRNA and CD4+ IL17A+ cell was observed in patients with SSc. Interestingly, the percentage of TH17 cells expressing CD146 was higher in patients with SSc and inversely correlated with pulmonary fibrosis. In vitro experiments showed an augmentation of the percentage of TH17 cells expressing CD146 after cell treatment with sCD146, suggesting that, in patients the increase of this sub-population could be the consequence of the sCD146 increase in serum. In conclusion, TH17 cells expressing CD146 could represent a new component of the adaptive immune response, opening the way for the generation of new tools for the management of SSc.

Highlights

Systemic sclerosis (SSc) is an autoimmune disorder characterized by vascular damage, excessive fibrosis and abnormal T cells immune-regulation
We recently reported a major role of CD146, a molecule ubiquitously distributed on vascular cells, and expressed on a subset of lymphocytes involved in the pathogenesis of the disease, TH17 cells
In this study we demonstrated for the time that TH17 lymphocytes expressing CD146 are increased in patients with SSc, suggesting their involvement in the pathology

Summary

Introduction

Systemic sclerosis (SSc) is an autoimmune disorder characterized by vascular damage, excessive fibrosis and abnormal T cells immune-regulation. TH17 cells expressing CD146 could represent a new component of the adaptive immune response, opening the way for the generation of new tools for the management of SSc. Systemic sclerosis (SSc) is an autoimmune disease characterized by excessive fibrosis in the skin and internal organs, vascular damage and immune dysfunction. CD146 has been recently proposed as a new molecular target in SSc4 This cell adhesion molecule, called MUC18 and MCAM, is a membrane glycoprotein belonging to the Immunoglobulin super family. SSc patients n = 50 Median age (years) Male/female Clinical Features Limited cutaneous form Diffuse cutaneous form* Ulcers, scars, gangrene Pulmonary fibrosis (PF) Pulmonary arterial Hypertension (PAH) Digestive involvement Kidney involvement Immunological Results Positive for anti-nuclear antibodies - centromeric staining (ACA) - positive for anti-topoisomerase I (anti-topo I)

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Conclusion