First Author | Miao R | Year | 2013 |
Journal | Immunol Cell Biol | Volume | 91 |
Issue | 5 | Pages | 368-76 |
PubMed ID | 23567898 | Mgi Jnum | J:288144 |
Mgi Id | MGI:6430010 | Doi | 10.1038/icb.2013.11 |
Citation | Miao R, et al. (2013) Targeted disruption of MCPIP1/Zc3h12a results in fatal inflammatory disease. Immunol Cell Biol 91(5):368-76 |
abstractText | Previous studies using MCP-induced protein 1 (MCPIP1)/Zc3h12a-deficient mice suggest that MCPIP1 is an important regulator of inflammation and immune homeostasis. However, the characterization of the immunological phenotype of MCPIP1-deficient mice has not been detailed. In this study, we performed evaluation through histological, flow cytometric, enzyme-linked immunosorbent assay and real-time PCR analysis and found that targeted disruption of MCPIP1 gene leads to fatal, highly aggressive and widespread immune-related lesions. In addition to previously observed growth retardation, splenomegaly, lymphoadenopathy, severe anemia and premature death, MCPIP1-deficient mice showed disorganization of lymphoid organs, including spleen, lymph nodes and thymus, and massive infiltration of lymphocytes, macrophages and neutrophils into many other non-lymphoid organs, primarily in lungs and liver. Flow cytometric analysis found significant increase in activated and differentiated T cells in peripheral blood and spleen of MCPIP1-deficient mice. Moreover, heightened production of inflammatory cytokines from activated macrophages and T cells were observed in MCPIP1-deficient mice. Interestingly, treatment of MCPIP1-deficient mice with antibiotics resulted in significant improvement of life span and a decrease in inflammatory syndrome. Taken together, these results suggest a prominent role for MCPIP1 in the control of inflammation and immune homeostasis. |