MiR-574-5p activates human TLR8 to promote autoimmune signaling and lupus
Wang, Tao (Xiamen University)
Song, Dan (Xiamen University)
Li, Xuejuan (Dalian Medical University (Xina))
Luo, Yu (The Third Military Medical University (Chongqing, Xina))
Yang, Dianqiang (Xiamen University)
Liu, Xiaoyan (Dalian Medical University (Xina))
Kong, Xiaodan (Dalian Medical University (Xina))
Xing, Yida (Dalian Medical University (Xina))
Bi, Shulin (Xiamen University)
Zhang, Yan (Xiamen University)
Hu, Tao (Xiamen University)
Zhang, Yunyun (Xiamen University)
Dai, Shugan (Xiamen University)
Shao, Zhiqiang (Xiamen University)
Chen, Dahan (Xiamen University)
Hou, Jinpao (Xiamen University)
Ballestar, Esteban (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Cai, Jianchun (Medical College of Xiamen University)
Zheng, Feng (Dalian Medical University)
Yang, James Y (East China Normal University)

Data:	2024
Resum:	Endosomal single-stranded RNA-sensing Toll-like receptor-7/8 (TLR7/8) plays a pivotal role in inflammation and immune responses and autoimmune diseases. However, the mechanisms underlying the initiation of the TLR7/8-mediated autoimmune signaling remain to be fully elucidated. Here, we demonstrate that miR-574-5p is aberrantly upregulated in tissues of lupus prone mice and in the plasma of lupus patients, with its expression levels correlating with the disease activity. miR-574-5p binds to and activates human hTLR8 or its murine ortholog mTlr7 to elicit a series of MyD88-dependent immune and inflammatory responses. These responses include the overproduction of cytokines and interferons, the activation of STAT1 signaling and B lymphocytes, and the production of autoantigens. In a transgenic mouse model, the induction of miR-574-5p overexpression is associated with increased secretion of antinuclear and anti-dsDNA antibodies, increased IgG and C3 deposit in the kidney, elevated expression of inflammatory genes in the spleen. In lupus-prone mice, lentivirus-mediated silencing of miR-574-5p significantly ameliorates major symptoms associated with lupus and lupus nephritis. Collectively, these results suggest that the miR-574-5p-hTLR8/mTlr7 signaling is an important axis of immune and inflammatory responses, contributing significantly to the development of lupus and lupus nephritis.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Toll-like receptor ; Mir-574-5p ; Htlr8 ; Autoimmunity ; Systemic lupus erythematosus ; Lupus nephritis
Publicat a:	Cell communication and signaling, Vol. 22 Núm. 1 (december 2024) , p. 220, ISSN 1478-811X

DOI: 10.1186/s12964-024-01601-1
PMID: 38589923

24 p, 3.7 MB

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Documents de recerca > Documents dels grups de recerca de la UAB > Centres i grups de recerca (producció científica) > Ciències de la salut i biociències > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Institut de Recerca contra la Leucèmia Josep Carreras
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