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Targeted disruption of MCPIP1/Zc3h12a results in fatal inflammatory disease.

ABSTRACT: 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.

SUBMITTER: Miao R

PROVIDER: S-EPMC3932977 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

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Targeted disruption of MCPIP1/Zc3h12a results in fatal inflammatory disease.

Miao Ruidong R Huang Shengping S Zhou Zhou Z Quinn Tim T Van Treeck Benjamin B Nayyar Tehreem T Dim Daniel D Jiang Zhisheng Z Papasian Christopher J CJ Eugene Chen Y Y Liu Gang G Fu Mingui M

Immunology and cell biology 20130409 5

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 w ...[more]

PMID: 23567898

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Targeted disruption of MCPIP1/Zc3h12a results in fatal inflammatory disease.

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Targeted disruption of MCPIP1/Zc3h12a results in fatal inflammatory disease.

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