Tripartite motif-containing protein 30 modulates TCR-activated proliferation and effector functions in CD4+ T cells

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

doi:10.1371/journal.pone.0095805

Tripartite motif-containing protein 30 modulates TCR-activated proliferation and effector functions in CD4+ T cells

PLoS One. 2014 Apr 22;9(4):e95805. doi: 10.1371/journal.pone.0095805. eCollection 2014.

Authors

Un Yung Choi¹, Ji Yeon Hur², Myeong Sup Lee¹, Quanri Zhang², Won Young Choi¹, Lark Kyun Kim¹, Wook-Bin Lee¹, Goo Taeg Oh³, Young-Joon Kim⁴

Affiliations

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.
⁴ Department of Biochemistry, College of Life Science and Technology, Yonsei University, Seoul, Korea; Department of Integrated Omics for Biomedical Science, WCU Program of Graduate School, Yonsei University, Seoul, Korea.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Age Factors
Animals
CD4-CD8 Ratio
CD4-Positive T-Lymphocytes / immunology*
CD4-Positive T-Lymphocytes / metabolism*
Carrier Proteins / genetics*
Carrier Proteins / metabolism
Cell Cycle / genetics
Homeodomain Proteins / genetics
Lymphocyte Activation / genetics*
Lymphocyte Activation / immunology*
Male
Mice
Mice, Knockout
NF-kappa B / metabolism
Receptors, Antigen, T-Cell / metabolism*

Substances

Carrier Proteins
Homeodomain Proteins
NF-kappa B
Receptors, Antigen, T-Cell
TRIM3 protein, mouse
RAG-1 protein

Grants and funding

This research was supported by the Global Research Laboratory Program of the National Research Foundation (NRF) funded by the Ministry of Science, ICT and Future Planning (MEST; K20705000006-12A0500-00610 to Y.-J.K.), the Bio and Medical Technology Development Program of the National Research Foundation (NRF) funded by the Ministry of Science, ICT and Future Planning (MEST; 2012028272 to Y.-J.K.), the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health and Welfare, Republic of Korea (grant number: HI13C08470200). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.