Deletion of the Mitochondrial Membrane Protein Fam210b Is Associated with the Development of Systemic Lupus Erythematosus

• Published in: International journal of molecular sciences Vol. 25; no. 13; p. 7253
• Main Authors: Xu, Yaqi, Gao, Ran, Zhang, Min, Zeng, Qi, Zhu, Gaizhi, Qiu, Jinming, Su, Wenting, Wang, Renxi
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.07.2024
• Subjects: Animals; Antibodies, Antinuclear; Antigens; Autoantibodies; autoantibody; Autoimmunity; B cells; Development and progression; Disease Models, Animal; erythroid cells; Erythroid Cells - metabolism; Erythroid Cells - pathology; Fam210b; Female; Immunoglobulin G - metabolism; Kinases; Lupus; Lupus Erythematosus, Systemic - genetics; Lupus Erythematosus, Systemic - metabolism; Lupus Erythematosus, Systemic - pathology; Lymphocytes; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Mitochondrial DNA; Mitochondrial Membranes - metabolism; Mitochondrial Proteins - genetics; Mitochondrial Proteins - metabolism; Reactive Oxygen Species - metabolism; Scientific equipment and supplies industry; single-cell sequencing; Spleen - metabolism; Spleen - pathology; Systemic lupus erythematosus; United States; China; single-cell sequencing; Fam210b; systemic lupus erythematosus; erythroid cells; autoantibody
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25137253

Mitochondrial dysfunction has been increasingly recognized as a trigger for systemic lupus erythematosus (SLE). Recent bioinformatics studies have suggested Fam210b as a significant candidate for the classification and therapeutic targeting of SLE. To experimentally prove the role of Fam210b in SLE, we constructed knockout ( ) mice using the CRISPR-Cas9 method. We found that approximately 15.68% of Fam210b mice spontaneously developed lupus-like autoimmunity, which was characterized by skin ulcerations, splenomegaly, and an increase in anti-double-stranded DNA (anti-dsDNA) IgG antibodies and anti-nuclear antibodies(ANA). Single-cell sequencing showed that was mainly expressed in erythroid cells. Critically, the knockout of resulted in abnormal erythrocyte differentiation and development in the spleens of mice. Concurrently, the spleens exhibited an increased number of CD71 erythroid cells, along with elevated levels of reactive oxygen species (ROS) in the erythrocytes. The co-culture of CD71 erythroid cells and lymphocytes resulted in lymphocyte activation and promoted dsDNA and IgG production. In summary, knockout leads to a low probability of lupus-like symptoms in mice through the overproduction of ROS in CD71 erythroid cells. Thus, Fam210b reduction may serve as a novel key marker that triggers the development of SLE.