title: Dysregulation of autoimmunity caused by silica exposure and alteration of Fas-mediated apoptosis in T lymphocytes derived from silicosis patients.
abstract: Silicosis patients suffer from pulmonary fibrosis caused by silica inhalation, as well as autoimmune diseases known as the adjuvant effects of silica. Caplan syndrome complicated with rheumatoid arthritis (RA) is well known epidemiologically, and the incidence of complicated systemic sclerosis (SSc), systemic lupus erythematosus (SLE) and antineutrophilic cytoplasmic antibody (ANCA)-related nephritis have been reported frequently in silicosis patients. To explore the detailed mechanisms of silica-induced dysregulation of autoimmunity, we had focused on Fas/CD95 and Fas-mediated apoptosis because Fas is one of the most important molecules regarding apoptosis of lymphocytes and its alteration makes some T cells survive longer. Additionally, if the long-survived T cells include the self-recognizing T-cell clones, it is easily thought that autoimmune diseases will appear in this situation. Furthermore, regulatory T cells (Treg) showing CD4+25+ and forkhead box P3 (FoxP3)-positive have been a central player in regulating activation of self- and foreign-antigen recognizing T cells, and it has been reported that activation of Treg causes its higher expression of Fas/CD95. Thus, in this review, we introduce the alteration of Fas and related molecules as found in silicosis and also present the Treg function of the CD4+25+ fraction in peripheral blood mononuclear cells derived from silicosis patients.
authors.affiliation: Department of Hygiene, Kawasaki Medical School, 577 Matsushima, Kurashiki 7010192, Japan. takemi@med.kawasaki-m.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Otsuki
authors.forename: H
authors.initials: H
authors.lastname: Hayashi
authors.forename: Y
authors.initials: Y
authors.lastname: Nishimura
authors.forename: F
authors.initials: F
authors.lastname: Hyodo
authors.forename: M
authors.initials: M
authors.lastname: Maeda
authors.forename: N
authors.initials: N
authors.lastname: Kumagai
authors.forename: Y
authors.initials: Y
authors.lastname: Miura
authors.forename: M
authors.initials: M
authors.lastname: Kusaka
authors.forename: K
authors.initials: K
authors.lastname: Uragami
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015551:Autoimmunity / Q000187:drug effects*; D006801:Humans; D012822:Silicon Dioxide / Q000633:toxicity*; D012829:Silicosis / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology; D019014:fas Receptor / Q000502:physiology*
chemical_list: D019014:fas Receptor; D012822:Silicon Dioxide