Zinc chloride may regulate hematopoietic stem cell aging and pro-inflammatory cytokines in systemic lupus erythematosus

Abstract

Background: The immune cells of patients with systemic lupus erythematosus (SLE) age earlier than those of normal subjects. However, the senescence of circulating hematopoietic stem cells (HSCs) in patients with SLE is not well understood, and it is unclear whether zinc treatment can regulate the senescence and proinflammatory cytokine production of HSCs in these patients. Methods: Clinical data were collected on 38 patients with SLE and 35 healthy controls (HCs), and the complete blood count, circulating HSC number, and p16 (a senescence marker) expression in the peripheral blood of these participants were analyzed via flow cytometry. Pooled circulating HSCs were isolated using leukapheresis. The effects of zinc chloride exposure on the pooled HSCs of each group were determined in vitro. Levels of the proinflammatory cytokines IL-6 and IL17, regulatory cytokine TGF-β, p16, and regulator T-cells (Tregs) were evaluated 72 h after incubation with 50 or 100 µM zinc chloride. Results: The number of circulating HSCs did not differ between the two groups (p=0.1685). The expression of p16 in HSCs was higher in the SLE group than in the HC group (p = 0.0043), and patients with SLE exhibited higher levels of IL-6, IL-17, and p16 in pooled HSCs (p =0.0025, p<0.0001, and p = 0.0003, respectively), although TGF-β levels did not differ between the groups (p=0.9816). Zinc chloride reduced IL-6, TGF-β, IL-17, and p16 expression in patients with SLE toward HC levels. Treg frequency in pooled HSCs was comparable between the groups (p=0.3997), although a 100 µM zinc chloride treatment significantly depleted the Treg population of patients with SLE (p=0.0001). Conclusions: Circulating HSCs in SLE are more aged and produce more proinflammatory cytokines. Zinc chloride treatment might prevent immunoaging and inhibit proinflammatory cytokine–producing cells in patients with SLE.