title: 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.
authors.affiliation: Department of Basic Medical Science, School of Medicine, University of Missouri-Kansas City, Kansas City, MO, USA.
authors.forename: Ruidong
authors.initials: R
authors.lastname: Miao
authors.forename: Shengping
authors.initials: S
authors.lastname: Huang
authors.forename: Zhou
authors.initials: Z
authors.lastname: Zhou
authors.forename: Tim
authors.initials: T
authors.lastname: Quinn
authors.forename: Benjamin
authors.initials: B
authors.lastname: Van Treeck
authors.forename: Tehreem
authors.initials: T
authors.lastname: Nayyar
authors.forename: Daniel
authors.initials: D
authors.lastname: Dim
authors.forename: Zhisheng
authors.initials: Z
authors.lastname: Jiang
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Papasian
authors.forename: Y
authors.initials: Y
authors.lastname: Eugene Chen
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.forename: Mingui
authors.initials: M
authors.lastname: Fu
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D064806:Dysbiosis / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects / Q000235:genetics; D007249:Inflammation / Q000235:genetics*; D008099:Liver / Q000276:immunology / Q000473:pathology; D008168:Lung / Q000276:immunology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D064307:Microbiota / Q000235:genetics / Q000276:immunology; D009092:Mucous Membrane / Q000276:immunology; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D020871:RNA Stability / Q000276:immunology; D012260:Ribonucleases; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D000900:Anti-Bacterial Agents; D053594:Myeloid Differentiation Factor 88; D014157:Transcription Factors; D012260:Ribonucleases; C510646:ZC3H12A protein, human