Relationship Between T-Cell Exosomes and Cellular Subsets in SLE According to Type I IFN-Signaling

Frontiers in Medicine

article

Patricia López¹  Javier Rodríguez-Carrio¹  Luis Caminal-Montero³  Ana Suárez¹ 

[1] Department of Functional Biology, Faculty of Medicine, University of Oviedo;Group of Basic and Translational Research in Inflammatory Diseases, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA);Department of Internal Medicine, Hospital Universitario Central de Asturias

关键词: exosomes;    senescent CD4 + CD28 null T cells;    systemic lupus erythematosus;    type I interferon (IFN);    cytokines;   

DOI  :  10.3389/fmed.2020.604098

学科分类：社会科学、人文和艺术（综合）

来源: Frontiers

【 摘 要 】

Objective: To quantify the levels of circulating exosomes derived from T-cells and monocytes and their possible associations with leukocyte subpopulations and cytokine milieu in Systemic Lupus Erythematosus (SLE). Methods: Total circulating exosomes (CD9 + -Ex) and those derived from T-cells (CD3 + -Ex) and monocytes (CD14 + -Ex) were quantified by flow cytometry in 82 SLE patients and 32 controls. Leukocyte subsets and serum cytokines were analyzed by flow cytometry or by immunoassays. IFN-score was evaluated by real time RT-PCR in whole blood samples from a subgroup of 73 patients and 24 controls. Results: Activation markers (IFNR1 and BLyS) on monocytes, neutrophils and B-cells correlated inversely with circulating exosomes (CD9 + -Ex, CD3 + -Ex, and CD14 + -Ex) in controls but directly with CD3 + -Ex in patients (all p < 0.05). Although CD9 + -Ex were increased in SLE, no differences were found in CD3 + -Ex, supporting that exosome content accounts for this opposite role. Interestingly, CD4 + CD28 null cells correlated with CD3 + -Ex in patients and controls, and displayed similar associations with leukocyte subsets in both groups. Additionally, CD3 + -Ex correlated in patients with the expression of CD25 in CD4 + CD28 null cells. Furthermore, the activated status of this senescent subset was related to IFNα serum levels in controls and to IFN-score in SLE patients. Finally, patients presenting high IFN-score, in addition to elevated CD25 + CD28 null cells associated with the activation of myeloid cells, displayed higher levels of inflammatory cytokines and chemokines. Conclusion: Our results support a relationship between T-cell exosomes and cellular subsets in SLE according to type I IFN-signaling, which could amplify chronic immune activation and excessive cytokine/chemokine response.

【 授权许可】

CC BY