Conditional Upregulation of IFN-α Alone Is Sufficient to Induce Systemic Lupus Erythematosus.

Autor:	Akiyama C; Department of Biophysics, Kobe University Graduate School of Health Science, Kobe 654-0142, Japan., Tsumiyama K; Department of Biophysics, Kobe University Graduate School of Health Science, Kobe 654-0142, Japan.; Institute for Rheumatic Diseases, Ashiya 659-0004, Japan.; Kyushu University Beppu Hospital, Beppu 874-0838, Japan; and., Uchimura C; Department of Biophysics, Kobe University Graduate School of Health Science, Kobe 654-0142, Japan., Honda E; Department of Biophysics, Kobe University Graduate School of Health Science, Kobe 654-0142, Japan., Miyazaki Y; Department of Biophysics, Kobe University Graduate School of Health Science, Kobe 654-0142, Japan., Sakurai K; Institute for Rheumatic Diseases, Ashiya 659-0004, Japan.; Kyushu University Beppu Hospital, Beppu 874-0838, Japan; and., Miura Y; Department of Biophysics, Kobe University Graduate School of Health Science, Kobe 654-0142, Japan., Hashiramoto A; Department of Biophysics, Kobe University Graduate School of Health Science, Kobe 654-0142, Japan., Felsher DW; Division of Oncology, Department of Medicine and Pathology, School of Medicine, Stanford University, Stanford, CA 94305., Shiozawa S; Department of Biophysics, Kobe University Graduate School of Health Science, Kobe 654-0142, Japan; shiozawa@port.kobe-u.ac.jp.; Institute for Rheumatic Diseases, Ashiya 659-0004, Japan.; Kyushu University Beppu Hospital, Beppu 874-0838, Japan; and.
Jazyk:	angličtina
Zdroj:	Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2019 Aug 15; Vol. 203 (4), pp. 835-843. Date of Electronic Publication: 2019 Jul 19.
DOI:	10.4049/jimmunol.1801617
Abstrakt:	The cause of systemic lupus erythematosus (SLE) is unknown. IFN-α has been suggested as a causative agent of SLE; however, it was not proven, and to what extent and how IFN-α contributes to the disease is unknown. We studied the contribution of IFN-α to SLE by generating inducible IFN-α transgenic mice and directly show that conditional upregulation of IFN-α alone induces a typical manifestation of SLE in the mice not prone to autoimmunity, such as serum immune complex, autoantibody against dsDNA (anti-dsDNA Ab), and the organ manifestations classical to SLE, such as immune complex-deposited glomerulonephritis, classical splenic onion-skin lesion, alopecia, epidermal liquefaction, and positive lupus band test of the skin. In the spleen of mice, activated effector CD4 T cells, IFN-γ-producing CD8 T cells, B220 + CD86 + cells, and CD11c + CD86 + cells were increased, and the T cells produced increased amounts of IL-4, IL-6, IL-17, and IFN-γ and decreased IL-2. In particular, activated CD3 + CD4 - CD8 - double-negative T cells positive for TCRαβ, B220, CD1d-teteramer, PD-1, and Helios (that produced increased amounts of IFN-γ, IL-4, IL-17, and TNF-α) were significantly expanded. They infiltrated into kidney and induced de novo glomerulonephritis and alopecia when transferred into naive recipients. Thus, sole upregulation of IFN-α is sufficient to induce SLE, and the double-negative T cells expanded by IFN-α are directly responsible for the organ manifestations, such as lupus skin disease or nephritis. (Copyright © 2019 by The American Association of Immunologists, Inc.)
Databáze:	MEDLINE
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