Environmental factors producing autoimmune dysregulation--chronic activation of T cells caused by silica exposure.
Autoimmune disorders are induced by various environmental and occupational substances. Among the most typical factors involving these substances, it is well known that silica exposure causes not only pulmonary fibrosis known as silicosis, but also induces autoimmune diseases such as rheumatoid arthritis known as Caplan's syndrome, systemic sclerosis, systemic lupus erythematosus, and anti-neutrophil cytoplasmic autoantibody (ANCA)-related vasculitis/nephritis. To investigate the immunological effects of silica, a focus on the occurrence of autoimmune dysfunction may clarify these autoimmune diseases and develop effective tools for observing silicosis patients (SIL). In this review, our investigation concerns the autoantibodies found in SIL, alteration of CD95/Fas and related molecules in SIL, case-oriented and in vitro analyses of silica-induced activation of responder and regulatory T cells, and supposed mechanisms of reduction of CD4+25+FoxP3+ regulatory T cells (T(reg)) in SIL. Further studies are required to investigate Th17 and the interaction with T(reg) in SIL to understand the cellular and molecular mechanisms of environmental and occupational autoimmune disorders.
Department of Hygiene, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192, Japan.
Suni
S
Lee
Hiroaki
H
Hayashi
Megumi
M
Maeda
Ying
Y
Chen
Hidenori
H
Matsuzaki
Naoko
N
Takei-Kumagai
Yasumitsu
Y
Nishimura
Wataru
W
Fujimoto
Takemi
T
Otsuki
D017209:Apoptosis; D001323:Autoantibodies / Q000096:biosynthesis / Q000276:immunology; D001327:Autoimmune Diseases / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D018791:CD4 Lymphocyte Count; D004781:Environmental Exposure / Q000009:adverse effects*; D006801:Humans; D008213:Lymphocyte Activation; D012822:Silicon Dioxide / Q000009:adverse effects / Q000276:immunology*; D012829:Silicosis / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology; D019014:fas Receptor / Q000096:biosynthesis / Q000276:immunology
D001323:Autoantibodies; D019014:fas Receptor; D012822:Silicon Dioxide