IL-10-Producing CD1dhiCD5+ Regulatory B Cells May Play a Critical Role in Modulating Immune Homeostasis in Silicosis Patients

Abstract

Silicosis is characterized by chronic lung inflammation and fibrosis, which are extremely harmful to human health. The pathogenesis of silicosis involves uncontrolled immune processes. Evidence supports that regulatory B cells (Bregs) produce negative regulatory cytokines, such as IL-10, which can negatively regulate immune responses in inflammation and autoimmune diseases. Our previous study found that IL-10-producing B cells were involved in the development of silica-induced lung inflammation and fibrosis of mice. However, little is known about the role of Bregs in silicosis patients (SP). In this study, we found that serum concentrations of IL-10 were significantly increased in SP by using protein array screening. We further determined that the frequency of IL-10-producing CD1dhiCD5+ Bregs, not IL-10-producing non-B lymphocytes, was significantly higher in SP compared to subjects under surveillance (SS) and healthy workers (HW) by flow cytometry. We also found that regulatory T cells (Tregs) and Th2 cytokines (IL-4, IL-5, and IL-13) were significantly increased in SP. Th1 cytokines (IFN-γ, IL-2, and IL-12) and inflammatory cytokines (IL-1β, IL-6, and TNF-α) were not significantly different between SP, SS, and HW. Our study indicated that IL-10-producing CD1dhiCD5+ Bregs might maintain Tregs and regulate Th1/Th2 polarization in SP, suggesting that IL-10-producing Bregs may play a critical role in modulating immune homeostasis in SP.

Regulatory B Cells Are Decreased and Impaired in Their Function in Peripheral Maternal Blood in Pre-term Birth

“…Besides their established phenotype in mice, the molecules CD5 and CD1d might also define a human Breg population (15,33,34). It is important to separate these cells from CD5expressing B1a B cells.…”

Emerging Role of Immunosuppression in Diseases Induced by Micro- and Nano-Particles: Time to Revisit the Exclusive Inflammatory Scenario

“…However, it is becoming evident that most available anti-inflammatory drugs ( 34 , 35 ) or cytokine inhibitor therapy ( 36 ) are not effective for particle-exposed patients. Human validation studies have also failed to confirm the use of inflammatory mediators as biomarkers for univocally detecting the health effects of particles ( 37 ).…”

“…However, several lines of evidence have demonstrated that IL-10 (as TGF-β) possesses deleterious and pro-fibrotic functions after particle exposure. First, lung expression of IL-10 was intimately associated to the development of particle-induced fibrosis and cancer and could explain the absence of chronic and progressive inflammation in human and mouse models ( 37 , 53 , 57 , 84 – 88 ). Additional data supports that IL-10 participates in the extension of fibrosis since targeted overexpression of IL-10 in the murine airways caused, by itself, collagen deposition, accumulation of mesenchymal cells and airway remodeling with fibrosis ( 89 , 90 ).…”

“…More recently, Chen and colleagues have identified an additional immunosuppressive subpopulation of B lymphocytes recruited in response to silica in human and animal ( 37 , 101 ) (Figure 2 ). Regulatory B-lymphocytes (B regs) are immunosuppressive cells releasing IL-10 and TGF-β that support immunological tolerance and suppress immunopathology by limiting the expansion of inflammatory T cells.…”

Inflammatory and oxidative stress biomarkers induced by silica exposure in crystal craftsmen

“…The activation and recruitment of macrophages and neutrophils into the lung parenchyma, particularly on the NALP-3 inflammasome, drives the production of inflammatory cytokines and chemokines, thus promoting and intensifying local tissue damage that culminates in collagen and elastin deposition and lung remodeling. [11][12][13][14][15] Among those mediators implicated in the pathogenesis of silicosis, the interleukins IL-1β, IL-4, IL-5, IL-6, IL-8, and IL-10 12, [16][17][18] ; tumor necrosis factor (TNF) and its receptor sTNFR1 and sTNFR2; transforming growth factor β (TGF-β), and the chemokines CCL3 and CCL24 have been highlighted. 19,20 Other inflammatory markers such as bone morphogenetic protein (BMP2) and chemokines CCL5 and CXCL16 have been shown to mediate vascular plasticity, angiogenesis, and leukocyte recruitment in distinct tissues 21,22 and, more recently, implicated in potentiating respiratory-inflammatory processes driven by T-cells and macrophages in asthma 23,24 and viral infections.…”