دورية أكاديمية
أعرض في EDS

Modulation of the Itaconate Pathway Attenuates Murine Lupus.

التفاصيل البيبلوغرافية
العنوان: Modulation of the Itaconate Pathway Attenuates Murine Lupus.
المؤلفون: Blanco LP; Systemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases NIH, Bethesda, Maryland., Patino-Martinez E; Systemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases NIH, Bethesda, Maryland., Nakabo S; Systemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases NIH, Bethesda, Maryland., Zhang M; Systemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases NIH, Bethesda, Maryland., Pedersen HL; Systemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases NIH, Bethesda, Maryland., Wang X; Systemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases NIH, Bethesda, Maryland., Carmona-Rivera C; Systemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases NIH, Bethesda, Maryland., Claybaugh D; Systemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases NIH, Bethesda, Maryland., Yu ZX; Pathology Core, National Heart, Lung, and Blood Institute, NIH, Bethesda, Maryland., Desta E; Laboratory of Animal Science Section, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland., Kaplan MJ; Systemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases NIH, Bethesda, Maryland.
المصدر: Arthritis & rheumatology (Hoboken, N.J.) [Arthritis Rheumatol] 2022 Dec; Vol. 74 (12), pp. 1971-1983. Date of Electronic Publication: 2022 Nov 06.
نوع المنشور: Journal Article; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Wiley Country of Publication: United States NLM ID: 101623795 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2326-5205 (Electronic) Linking ISSN: 23265191 NLM ISO Abbreviation: Arthritis Rheumatol Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Malden, MA : Wiley, [2014]-
مواضيع طبية MeSH: Lupus Erythematosus, Systemic*/drug therapy, Mice ; Female ; Humans ; Animals ; Infant, Newborn ; Mice, Inbred NZB ; Disease Models, Animal ; Antibodies, Antinuclear
مستخلص: Objective: Itaconic acid, a Krebs cycle-derived immunometabolite, is synthesized by myeloid cells in response to danger signals to control inflammasome activation, type I interferon (IFN) responses, and oxidative stress. As these pathways are dysregulated in systemic lupus erythematosus (SLE), we investigated the role of an itaconic acid derivative in the treatment of established murine lupus.
Methods: Female (NZW × NZB)F 1 lupus-prone mice were administered 4-octyl itaconate (4-OI) or vehicle starting after clinical onset of disease (30 weeks of age) for 4 weeks (n = 10 mice /group). At 34 weeks of age (peak disease activity), animals were euthanized, organs and serum were collected, and clinical, metabolic, and immunologic parameters were evaluated.
Results: Proteinuria, kidney immune complex deposition, renal scores of severity and inflammation, and anti-RNP autoantibodies were significantly reduced in the 4-OI treatment group compared to the vehicle group. Splenomegaly decreased in the 4-OI group compared to vehicle, with decreases in activation markers in innate and adaptive immune cells, increases in CD8+ T cell numbers, and inhibition of JAK1 activation. Gene expression analysis in splenocytes showed significant decreases in type I IFN and proinflammatory cytokine genes and increased Treg cell-associated markers in the 4-OI group compared to the vehicle group. In human control and lupus myeloid cells, 4-OI in vitro treatment decreased proinflammatory responses and B cell responses.
Conclusions: These results support targeting immunometabolism as a potentially viable approach in autoimmune disease treatment, with 4-OI displaying beneficial roles attenuating immune dysregulation and organ damage in lupus.
(Published 2022. This article is a U.S. Government work and is in the public domain in the USA.)
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معلومات مُعتمدة: ZIA AR041199 United States ImNIH Intramural NIH HHS; ZIA-AR-041199 United States AR NIAMS NIH HHS
المشرفين على المادة: Q4516562YH (itaconic acid)
0 (Antibodies, Antinuclear)
تواريخ الأحداث: Date Created: 20220706 Date Completed: 20221216 Latest Revision: 20240822
رمز التحديث: 20240822
مُعرف محوري في PubMed: PMC11337117
DOI: 10.1002/art.42284
PMID: 35791960
قاعدة البيانات: MEDLINE
الوصف
تدمد:2326-5205
DOI:10.1002/art.42284