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Monday, March 19, 2012: 14:15
Gran Cancun 4 (Cancun Center)
Takemi Otsuki, Department of Hygiene, Kawasaki Medical School, Kurashiki, Japan
Introduction
It is well known that silicosis patients (SILs) suffer from pulmonary dysfunction, including complications of autoimmune diseases such as rheumatoid arthritis (known as Caplan’s syndrome), systemic lupus erythematosus (SLE), systemic scleroderma (SSc), and anti-neutrophil cytoplasmic autoantibody (ANCA)-related vasculitis/nephritis. The effect of silica on the human immune system has been considered a result of the potential adjuvant ability of silica. However, recent developments in immunology should prompt a re-evaluation of the effects of silica on the general immune system, particularly T cell systems. Dysfunction of Fas/CD95, the well-known apoptosis receptor, is known to result in autoimmune disorders. Additionally, the discovery of regulatory T cells (Treg) has become a key point for consideration of the pathophysiology of autoimmune dysregulation. In this article, the dysregulation of the CD95/Fas molecule and modified activation of regulatory and effector T cells in SILs are described, and the effects of silica on dysregulation of autoimmunity are discussed.
Methods
CD4+25+FoxP3+ peripheral blood Treg derived from SIL and healthy donors (HD) were collected and examined their CD95/Fas expression as well as treg function was analyzed. In addition Cd4+25- effector T cells (Teff) from HD were cultured with silica and alterations of CD25 and FoxP3 expression were analyzed. As the activated marker, Cd4+25+ or 25- T cells from HD and SIL were measured their PD-1 and CD69 expression.
Result
CD95/Fas expression in Treg from SIL was higher than that from HD and Treg function was decreased inSIL. PD-1 from either CD25+ and CD25- cells was higher than that from HD. CD69 was higher in both fractions from SIL. In vitro exposure caused exhansing Fas/CD and CD25 expression.
Discussion
Silica can chronically activate both Treg and Teff and peripheral CD4+25+ fraction may exchanged from Treg to activated Teff, since early loss of CD95/Fas induced apotosis of Treg.
It is well known that silicosis patients (SILs) suffer from pulmonary dysfunction, including complications of autoimmune diseases such as rheumatoid arthritis (known as Caplan’s syndrome), systemic lupus erythematosus (SLE), systemic scleroderma (SSc), and anti-neutrophil cytoplasmic autoantibody (ANCA)-related vasculitis/nephritis. The effect of silica on the human immune system has been considered a result of the potential adjuvant ability of silica. However, recent developments in immunology should prompt a re-evaluation of the effects of silica on the general immune system, particularly T cell systems. Dysfunction of Fas/CD95, the well-known apoptosis receptor, is known to result in autoimmune disorders. Additionally, the discovery of regulatory T cells (Treg) has become a key point for consideration of the pathophysiology of autoimmune dysregulation. In this article, the dysregulation of the CD95/Fas molecule and modified activation of regulatory and effector T cells in SILs are described, and the effects of silica on dysregulation of autoimmunity are discussed.
Methods
CD4+25+FoxP3+ peripheral blood Treg derived from SIL and healthy donors (HD) were collected and examined their CD95/Fas expression as well as treg function was analyzed. In addition Cd4+25- effector T cells (Teff) from HD were cultured with silica and alterations of CD25 and FoxP3 expression were analyzed. As the activated marker, Cd4+25+ or 25- T cells from HD and SIL were measured their PD-1 and CD69 expression.
Result
CD95/Fas expression in Treg from SIL was higher than that from HD and Treg function was decreased inSIL. PD-1 from either CD25+ and CD25- cells was higher than that from HD. CD69 was higher in both fractions from SIL. In vitro exposure caused exhansing Fas/CD and CD25 expression.
Discussion
Silica can chronically activate both Treg and Teff and peripheral CD4+25+ fraction may exchanged from Treg to activated Teff, since early loss of CD95/Fas induced apotosis of Treg.