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.
Copyright © 2019 Elsevier Inc. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Calcium / immunology
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Calcium / metabolism
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Cell Differentiation / drug effects
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Cytokines / genetics
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Cytokines / immunology
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Cytokines / pharmacology*
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Female
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Gene Expression Regulation
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Immunophenotyping
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Ion Transport / drug effects
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Lymphocyte Activation / drug effects*
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Membrane Microdomains / drug effects*
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Membrane Microdomains / immunology
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Membrane Microdomains / metabolism
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Mice
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Mice, Inbred C57BL
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Phosphatidylinositol 3-Kinase / genetics
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Phosphatidylinositol 3-Kinase / immunology
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Phospholipase C gamma / genetics
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Phospholipase C gamma / immunology
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Phosphorylation / drug effects
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Primary Cell Culture
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Receptors, Antigen, T-Cell / antagonists & inhibitors
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Receptors, Antigen, T-Cell / genetics*
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Receptors, Antigen, T-Cell / immunology
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Signal Transduction / drug effects*
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Signal Transduction / genetics
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Signal Transduction / immunology
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T-Lymphocytes, Helper-Inducer / cytology
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T-Lymphocytes, Helper-Inducer / drug effects
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T-Lymphocytes, Helper-Inducer / immunology
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T-Lymphocytes, Regulatory / cytology
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T-Lymphocytes, Regulatory / drug effects*
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T-Lymphocytes, Regulatory / immunology
Substances
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Aimp1 protein, mouse
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Cytokines
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Receptors, Antigen, T-Cell
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Phosphatidylinositol 3-Kinase
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Phospholipase C gamma
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Calcium