AIMP1 regulates TCR signaling and induces differentiation of regulatory T cells by interfering with lipid raft association

Myun Soo Kim; Arim Lee; Daeho Cho; Tae Sung Kim

doi:10.1016/j.bbrc.2019.05.040

AIMP1 regulates TCR signaling and induces differentiation of regulatory T cells by interfering with lipid raft association

Biochem Biophys Res Commun. 2019 Jun 30;514(3):875-880. doi: 10.1016/j.bbrc.2019.05.040. Epub 2019 May 10.

Authors

Myun Soo Kim¹, Arim Lee², Daeho Cho¹, Tae Sung Kim³

Affiliations

¹ Institute of Convergence Science, Korea University, 5-ga, Anam-dong, Seongbuk-gu, Seoul, 02841, Republic of Korea.
² Division of Life Sciences, College of Life Sciences and Biotechnology, Korea University, 5-ga, Anam-dong, Seongbuk-gu, Seoul, 02841, Republic of Korea.
³ Division of Life Sciences, College of Life Sciences and Biotechnology, Korea University, 5-ga, Anam-dong, Seongbuk-gu, Seoul, 02841, Republic of Korea. Electronic address: tskim@korea.ac.kr.

PMID: 31084930
DOI: 10.1016/j.bbrc.2019.05.040

Abstract

In addition to a role in translation, AIMP1 is secreted to affect various immune cells, such as macrophages, dendritic cells, B cells, and natural killer cells. However, the direct effects of AIMP1 on T cells have not yet been reported. In this study, we investigated whether AIMP1 could modulate T cell responses directly. Results revealed that AIMP1 significantly inhibited T cell receptor (TCR)-dependent activation and proliferation of CD4 T cells, as well as decreased TCR stimuli-induced Ca²⁺ influx in CD4 T cells. In addition, microscopic analysis revealed that lipid raft association in response to TCR engagement was significantly reduced in the presence of AIMP1, and the phosphorylation of PLCγ and PI3K was also down-regulated in CD4 T cells by AIMP1. Furthermore, AIMP1 specifically enhanced the differentiation of regulatory T (Treg) cells, while it had no effect on T helper type 1 (Th1), type 2 (Th2), and type 17 (Th17) cell differentiation. Collectively, these results indicate that AIMP1 affects T cells directly by down-regulating TCR signaling complex formation and inducing Treg cell differentiation in CD4 T cells.

Keywords: AIMP1; Calcium flux; Lipid raft; TCR signal.

Publication types

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

MeSH terms

Animals
Calcium / immunology
Calcium / metabolism
Cell Differentiation / drug effects
Cytokines / genetics
Cytokines / immunology
Cytokines / pharmacology*
Female
Gene Expression Regulation
Immunophenotyping
Ion Transport / drug effects
Lymphocyte Activation / drug effects*
Membrane Microdomains / drug effects*
Membrane Microdomains / immunology
Membrane Microdomains / metabolism
Mice
Mice, Inbred C57BL
Phosphatidylinositol 3-Kinase / genetics
Phosphatidylinositol 3-Kinase / immunology
Phospholipase C gamma / genetics
Phospholipase C gamma / immunology
Phosphorylation / drug effects
Primary Cell Culture
Receptors, Antigen, T-Cell / antagonists & inhibitors
Receptors, Antigen, T-Cell / genetics*
Receptors, Antigen, T-Cell / immunology
Signal Transduction / drug effects*
Signal Transduction / genetics
Signal Transduction / immunology
T-Lymphocytes, Helper-Inducer / cytology
T-Lymphocytes, Helper-Inducer / drug effects
T-Lymphocytes, Helper-Inducer / immunology
T-Lymphocytes, Regulatory / cytology
T-Lymphocytes, Regulatory / drug effects*
T-Lymphocytes, Regulatory / immunology

Substances

Aimp1 protein, mouse
Cytokines
Receptors, Antigen, T-Cell
Phosphatidylinositol 3-Kinase
Phospholipase C gamma
Calcium