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The Role of Estrogen Membrane Receptor (G Protein-Coupled Estrogen Receptor 1) in Skin Inflammation Induced by Systemic Lupus Erythematosus Serum IgG.

ABSTRACT: Skin injury is the second most common clinical manifestation in patients with systemic lupus erythematosus (SLE). Estrogen may affect the onset and development of SLE through its receptor. In this study, we investigated the role of estrogen membrane receptor G protein-coupled estrogen receptor 1 (GPER1) in skin injury of SLE. We found that skin injury induced by SLE serum was more severe in female mice and required monocytes. Estrogen promoted activation of monocytes induced by lupus IgG through the membrane receptor GPER1 which was located in lipid rafts. Blockade of GPER1 and lipid rafts reduced skin inflammation induced by SLE serum. The results we obtained suggest that GPER1 plays an important role in the pathogenesis of skin inflammation induced by lupus IgG and might be a therapeutic target in skin lesions of patients with SLE.

SUBMITTER: Cai Z

PROVIDER: S-EPMC5722986 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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The Role of Estrogen Membrane Receptor (G Protein-Coupled Estrogen Receptor 1) in Skin Inflammation Induced by Systemic Lupus Erythematosus Serum IgG.

Cai Zhenming Z Xie Changhao C Qiao Wei W Fei Xibin X Guo Xuanxuan X Liu Huicheng H Li Xiaoyan X Fang Xiang X Xu Guangqiong G Dou Hui H Deng Guo-Min GM

Frontiers in immunology 20171204

Skin injury is the second most common clinical manifestation in patients with systemic lupus erythematosus (SLE). Estrogen may affect the onset and development of SLE through its receptor. In this study, we investigated the role of estrogen membrane receptor G protein-coupled estrogen receptor 1 (GPER1) in skin injury of SLE. We found that skin injury induced by SLE serum was more severe in female mice and required monocytes. Estrogen promoted activation of monocytes induced by lupus IgG through ...[more]

PMID: 29255468

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Project description:Systemic lupus erythematosus is a chronic autoimmune disease with multifactorial ethiopathogenesis. The complement system is involved in both the early and late stages of disease development and organ damage. To better understand autoantibody mediated complement consumption the GAPAID consortium examined ex vivo immune complex formation on autoantigen arrays. We recruited patients with SLE (n=211), with other systemic autoimmune diseases (n=65) and non-autoimmune control subjects (n=149) in two rheumatology tertiary care centers. Standard clinical and laboratory data were collected from all subjects and serum complement levels were determined in SLE patients. The genotype of SNP rs1143679 in the ITGAM gene was also determined. On-chip formation of immune complexes was examined using a functional immunoassay on autoantigen microarray. The amount of antigen-bound IgM, IgG and complement C4 and C3 was quantified on autoantigens comprising nucleic acids, proteins and lipids. Our results show that the relatively high complement consumption of nucleic acids is further increased upon binding of IgM and IgG. This is true even when serum complement levels are decreased due to complement consumption in SLE patients. A negative correlation between serum complement levels and ex vivo complement deposition on nucleic acid autoantigens is demonstrated. On the contrary, most protein and lipid autoantigens show positive correlation with C4 and C3 levels. Genetic analysis reveals that the non-synonymous variant rs1143679 in complement receptor type 3 is associated with an increased production of anti-dsDNA IgG antibodies. Notwithstanding, homozygous carriers of the previously reported susceptible allele (AA) have lower levels of dsDNA specific IgM among SLE patients. Regarding organ involvement we find that besides anti-C1q IgG, low levels of dsDNA specific IgM and low complement C4 binding to C1q are also associated with renal injury. In summary, nucleic acids maintain a skewed complement deposition balance when bound by IgG and IgM, depleting the early classical complement pathway from other physiological processes. Dysfunction of the receptor responsible for complement-mediated apoptotic debris removal promotes the development of autoantibodies targeting nucleic acids. These observations provide serological and genetic evidence for complement-mediated clearance deficiency of apoptotic debris in lupus.

Dataset Information

The Role of Estrogen Membrane Receptor (G Protein-Coupled Estrogen Receptor 1) in Skin Inflammation Induced by Systemic Lupus Erythematosus Serum IgG.

Publications

The Role of Estrogen Membrane Receptor (G Protein-Coupled Estrogen Receptor 1) in Skin Inflammation Induced by Systemic Lupus Erythematosus Serum IgG.

Similar Datasets

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