Tripartite Motif-Containing Protein 30 Modulates TCR-Activated Proliferation and Effector Functions in CD4+ T Cells |
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Authors: | Un Yung Choi Ji Yeon Hur Myeong Sup Lee Quanri Zhang Won Young Choi Lark Kyun Kim Wook-Bin Lee Goo Taeg Oh Young-Joon Kim |
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Affiliation: | 1. Department of Biochemistry, College of Life Science and Technology, Yonsei University, Seoul, Korea.; 2. Department of Integrated Omics for Biomedical Science, WCU Program of Graduate School, Yonsei University, Seoul, Korea.; 3. Division of Life and Pharmaceutical Sciences, Ewha Women’s University, Seoul, Korea.; Yonsei University, Republic of Korea, |
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Abstract: | To avoid excessive activation, immune signals are tightly controlled by diverse inhibitory proteins. TRIM30, a tripartite motif (TRIM)-containing protein is one of such inhibitors known to function in macrophages. To define the roles of TRIM30, we generated Trim30 knockout (Trim30−/−) mice. Trim30 deletion caused no major developmental defects in any organs, nor showed any discernable defect in the activation of macrophages. But, Trim30−/− mice showed increased CD4/CD8 ratio when aged and Trim30−/− CD4+ T cells exhibited an abnormal response upon TCR activation, in particular in the absence of a costimulatory signal. Adoptive transfer of wild-type and Trim30−/− CD4+ T cells together into lymphopenic hosts confirmed higher proliferation of the Trim30−/− CD4+ T cells in vivo. Despite the enhanced proliferation, Trim30−/− T cells showed decreased levels of NF-κB activation and IL-2 production compared to wild-type cells. These results indicate a distinct requirement for TRIM30 in modulation of NF-κB activation and cell proliferation induced by TCR stimulation. |
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