Date Published: December 6, 2013
Publisher: Public Library of Science
Author(s): Zhou Zhou, Ruidong Miao, Shengping Huang, Brandon Elder, Tim Quinn, Christopher J. Papasian, Jifeng Zhang, Daping Fan, Y. Eugene Chen, Mingui Fu, Deyu Fang.
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.
Anemia is a group of red blood cell (RBC) dysfunction or loss related diseases, which is caused by many reasons and mechanisms. Autoimmune gastritis is an organ-specific disease that is the underlying pathologic cause of vitamin B12 deficiency, the most common cause of pernicious anemia. The pathogenesis of autoimmune gastritis and its associated pernicious anemia is not completely understood due to lack of optimal animal models for this disease.
Anemia is a common disease of RBC deficiency. Previous reports described an anemia phenotype in MCPIP1-/- mice. However, the underlying mechanisms have not been reported. In the present study, we found that MCPIP1 deficiency in mice resulted in severe anemia related to autoimmune mechanisms. MCPIP1 deficiency did not affect erythropoiesis per se. In contrast, the MCPIP1-/- mice developed autoimmune gastritis and parietal cell loss. The consequent malfunction of iron and VB12 absorption finally lead to pernicious anemia. Thus, the MCPIP1-/- mice might be a model for the study of autoimmune gastritis against parietal cells, and pernicious anemia. In addition, MCPIP1 deficiency also led to the production of anti-RBC autoimmune antibody and probable hemolytic anemia. Our present work provided evidence of an immune regulatory role of MCPIP1 and the significance of preventing autoimmunity related anemia.
We are here reporting the underlying mechanisms of the anemia phenotype of MCPIP1-/- mice. We provided evidence that the anemia phenotype of MCPIP1-/- mice was caused by iron deficiency, VB12 deficiency and RBC rapid clearance, which was mainly resulted from autoimmune-associated gastritis and hemolysis. MCPIP1-/- mice may be a good mouse model for investigating the pathogenesis and possible treatment of autoimmune gastritis and pernicious anemia.