MCPIP1 deficiency in mice results in severe anemia related to autoimmune mechanisms

• Published in: PloS one 2013-12, Vol.8 (12), p.e82542-e82542
• Main Authors: Zhou, Zhou, Miao, Ruidong, Huang, Shengping, Elder, Brandon, Quinn, Tim, Papasian, Christopher J, Zhang, Jifeng, Fan, Daping, Chen, Y Eugene, Fu, Mingui
• Format: Article
• Language: English
• Subjects: Analysis; Anemia; Anemia - genetics; Anemia - immunology; Anemia - metabolism; Anemia - pathology; Anemia, Iron-Deficiency - genetics; Anemia, Iron-Deficiency - immunology; Anemia, Iron-Deficiency - metabolism; Animals; Autoantibodies - immunology; Autoimmune Diseases - genetics; Autoimmune Diseases - immunology; Autoimmune Diseases - pathology; Autoimmunity; Blood; Bone marrow; Bone Marrow - pathology; Cyanocobalamin; Disease Models, Animal; Drugs; Erythroblasts; Erythrocytes - immunology; Erythropoiesis; Erythropoiesis - genetics; Flow cytometry; Gastritis; Gastritis - genetics; Gastritis - immunology; Gastritis - pathology; Genetic Association Studies; Homeostasis; Immunoglobulins; Immunosuppressive agents; Inflammation; Internal medicine; Iron; Liver - metabolism; Liver - pathology; Male; Mammals; Medical treatment; Medicine; Mice; Mice, Knockout; Nutrient deficiency; Parietal Cells, Gastric - metabolism; Parietal Cells, Gastric - pathology; Pathogenesis; Pernicious anemia; Proteins; Ribonucleases - deficiency; Ribonucleases - genetics; Ribonucleases - metabolism; Rodents; Science; Signal transduction; Spleen - metabolism; Spleen - pathology; Stomach; Vitamin B 12 Deficiency; Vitamin B12
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0082542

Autoimmune gastritis is an organ-specific autoimmune disease of the stomach associated with pernicious anemia. The previous work from us and other groups identified MCPIP1 as an essential factor controlling inflammation and immune homeostasis. MCPIP1(-/-) developed severe anemia. However, the mechanisms underlying this phenotype remain unclear. In the present study, we found that MCPIP1 deficiency in mice resulted in severe anemia related to autoimmune mechanisms. Although MCPIP1 deficiency did not affect erythropoiesis per se, the erythropoiesis in MCPIP1(-/-) bone marrow erythroblasts was significantly attenuated due to iron and vitamin B12 (VB12) deficiency, which was mainly resulted from autoimmunity-associated gastritis and parietal cell loss. Consistently, exogenous supplement of iron and VB12 greatly improved the anemia phenotype of MCPIP1(-/-) mice. Finally, we have evidence suggesting that autoimmune hemolysis may also contribute to anemia phenotype of MCPIP1(-/-) mice. Taken together, our study suggests that MCPIP1 deficiency in mice leads to the development of autoimmune gastritis and pernicious anemia. Thus, MCPIP1(-/-) mice may be a good mouse model for investigating the pathogenesis of pernicious anemia and testing the efficacy of some potential drugs for treatment of this disease.