The lupus susceptibility allele DRB1*03:01 encodes a disease-driving epitope.
The lupus susceptibility allele DRB1*03:01 encodes a disease-driving epitope.
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狼疮易感性等位基因DRB1*03：01编码疾病的表位。
DOI：
10.1038/s42003-022-03717-x
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发表时间：
2022-07-28
影响因子：
5.9
通讯作者：
中科院分区：
文献类型：
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作者：
The HLA-DRB1*03:01 allele is a major genetic risk factor in systemic lupus erythematosus (SLE), but the mechanistic basis of the association is unclear. Here we show that in the presence of interferon gamma (IFN-γ), a short DRB1*03:01-encoded allelic epitope activates a characteristic lupus transcriptome in mouse and human macrophages. It also triggers a cascade of SLE-associated cellular aberrations, including endoplasmic reticulum stress, unfolded protein response, mitochondrial dysfunction, necroptotic cell death, and production of pro-inflammatory cytokines. Parenteral administration of IFN-γ to naïve DRB1*03:01 transgenic mice causes increased serum levels of anti-double stranded DNA antibodies, glomerular immune complex deposition and histopathological renal changes that resemble human lupus nephritis. This study provides evidence for a noncanonical, antigen presentation-independent mechanism of HLA-disease association in SLE and could lay new foundations for our understanding of key molecular mechanisms that trigger and propagate this devastating autoimmune disease. In the presence of IFN-γ, a short DRB1*03:01-encoded allelic epitope is found to activate a characteristic lupus transcriptome in macrophages and trigger a cascade of systemic lupus erythematosus-associated cellular aberrations.
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影响因子：
12.8
作者：
Ghodke-Puranik Y;Niewold TB
通讯作者：
Niewold TB
影响因子：
4.5
作者：
Barcellos LF;May SL;Ramsay PP;Quach HL;Lane JA;Nititham J;Noble JA;Taylor KE;Quach DL;Chung SA;Kelly JA;Moser KL;Behrens TW;Seldin MF;Thomson G;Harley JB;Gaffney PM;Criswell LA
通讯作者：
Criswell LA
影响因子：
14.9
作者：
Babicki S;Arndt D;Marcu A;Liang Y;Grant JR;Maciejewski A;Wishart DS
通讯作者：
Wishart DS
影响因子：
2.7
作者：
Choi Y;Jung JH;Lee EG;Kim KM;Yoo WH
通讯作者：
Yoo WH
DOI：
10.1084/jem.20201138
发表时间：
2021-05-03
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hartl J;Serpas L;Wang Y;Rashidfarrokhi A;Perez OA;Sally B;Sisirak V;Soni C;Khodadadi-Jamayran A;Tsirigos A;Caiello I;Bracaglia C;Volpi S;Ghiggeri GM;Chida AS;Sanz I;Kim MY;Belmont HM;Silverman GJ;Clancy RM;Izmirly PM;Buyon JP;Reizis B
通讯作者：
Reizis B