Publications by authors named "Dongjin Jeong"

6 Publications

  • Page 1 of 1

Ssu72 phosphatase directly binds to ZAP-70, thereby providing fine-tuning of TCR signaling and preventing spontaneous inflammation.

Proc Natl Acad Sci U S A 2021 08;118(35)

Laboratory of Immune Regulation, Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea;

ZAP-70 is required for the initiation of T cell receptor (TCR) signaling, and Ssu72 is a phosphatase that regulates RNA polymerase II activity in the nucleus. However, the mechanism by which ZAP-70 regulates the fine-tuning of TCR signaling remains elusive. Here, we found that Ssu72 contributed to the fine-tuning of TCR signaling by acting as tyrosine phosphatase for ZAP-70. Affinity purification-mass spectrometry and an in vitro assay demonstrated specific interaction between Ssu72 and ZAP-70 in T cells. Upon TCR stimulation, Ssu72-deficient T cells increased the phosphorylation of ZAP-70 and downstream molecules and exhibited hyperresponsiveness, which was restored by reducing ZAP-70 phosphorylation. In vitro assay demonstrated that recombinant Ssu72 reduced tyrosine phosphorylation of ZAP-70 via phosphatase activity. -Cre mice showed a defect in the thymic development of invariant natural killer T cells and reductions in CD4 and CD8 T cell numbers in the periphery but more CD44CD62L memory T cells and fewer CD44CD62L naïve T cells, compared with wild-type mice. Furthermore, -Cre mice developed spontaneous inflammation at 6 mo. In conclusion, Ssu72 phosphatase regulates the fine-tuning of TCR signaling by binding to ZAP-70 and regulating its tyrosine phosphorylation, thereby preventing spontaneous inflammation.
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http://dx.doi.org/10.1073/pnas.2102374118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8536320PMC
August 2021

Soluble Fas ligand drives autoantibody-induced arthritis by binding to DR5/TRAIL-R2.

Elife 2021 07 5;10. Epub 2021 Jul 5.

Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea.

To date, no study has demonstrated that soluble Fas ligand (sFasL)-mediated inflammation is regulated via interaction with Fas in vivo. We found that FasL interacts specifically with tumor necrosis factor receptor superfamily (TNFRSF)10B, also known as death receptor (DR)5. Autoantibody-induced arthritis (AIA) was attenuated in FasL ()- and soluble FasL ()-deficient mice, but not in Fas ( and )- or membrane FasL ()-deficient mice, suggesting sFasL promotes inflammation by binding to a Fas-independent receptor. Affinity purification mass spectrometry analysis using human (h) fibroblast-like synovial cells (FLSCs) identified DR5 as one of several proteins that could be the elusive Fas-independent FasL receptor. Subsequent cellular and biochemical analyses revealed that DR5 interacted specifically with recombinant FasL-Fc protein, although the strength of this interaction was approximately 60-fold lower than the affinity between TRAIL and DR5. A microarray assay using joint tissues from mice with arthritis implied that the chemokine CX3CL1 may play an important downstream role of the interaction. The interaction enhanced transcription and increased sCX3CL1 production in FLSCs, possibly in an NF-κB-dependent manner. Moreover, the sFasL-DR5 interaction-mediated CX3CL1-CX3CR1 axis initiated and amplified inflammation by enhancing inflammatory cell influx and aggravating inflammation via secondary chemokine production. Blockade of FasL or CX3CR1 attenuated AIA. Therefore, the sFasL-DR5 interaction promotes inflammation and is a potential therapeutic target.
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http://dx.doi.org/10.7554/eLife.48840DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257255PMC
July 2021

Development and Functions of Alveolar Macrophages.

Mol Cells 2021 May;44(5):292-300

Department of Pathology, Seoul National University College of Medicine, Seoul 03080, Korea.

Macrophages residing in various tissue types are unique in terms of their anatomical locations, ontogenies, developmental pathways, gene expression patterns, and immunological functions. Alveolar macrophages (AMs) reside in the alveolar lumen of the lungs and serve as the first line of defense for the respiratory tract. The immunological functions of AMs are implicated in the pathogenesis of various pulmonary diseases such as allergic asthma, chronic obstructive pulmonary disorder (COPD), pulmonary alveolar proteinosis (PAP), viral infection, and bacterial infection. Thus, the molecular mechanisms driving the development and function of AMs have been extensively investigated. In this review article, we discuss the roles of granulocyte-macrophage colony-stimulating factor (GM-CSF) and transforming growth factor (TGF)-β in AM development, and provide an overview of the anti-inflammatory and proinflammatory functions of AMs in various contexts. Notably, we examine the relationships between the metabolic status of AMs and their development processes and functions. We hope that this review will provide new information and insight into AM development and function.
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http://dx.doi.org/10.14348/molcells.2021.0058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175155PMC
May 2021

Sodium chloride inhibits IFN-γ, but not IL-4, production by invariant NKT cells.

J Leukoc Biol 2018 01 19;103(1):99-106. Epub 2017 Dec 19.

Laboratory of Immune Regulation, Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.

Invariant NKT (iNKT) cells are a distinct subset of T cells that exert Janus-like functions in vivo by producing IFN-γ and IL-4. Sodium chloride modulates the functions of various immune cells, including conventional CD4 T cells and macrophages. However, it is not known whether sodium chloride affects iNKT cell function, so we addressed this issue. Sodium chloride inhibited IFN-γ, but not IL-4, production by iNKT cells upon TCR or TCR-independent (IL-12 and IL-18) stimulation in a dose-dependent manner. Consistently, sodium chloride reduced the expression level of tbx21, but not gata-3, in iNKT cells stimulated with TCR engagement or IL-12 + IL-18. Sodium chloride increased phosphorylated p38 expression in iNKT cells and inhibitors of p38, NFAT5, SGK1, and TCF-1 restored IFN-γ production by iNKT cells stimulated with sodium chloride and TCR engagement. Furthermore, adoptive transfer of iNKT cells pretreated with sodium chloride restored antibody-induced joint inflammation to a lesser extent than for untreated iNKT cells in Jα18 knockout mice. These findings suggest that sodium chloride inhibits IFN-γ production by iNKT cells in TCR-dependent and TCR-independent manners, which is dependent on p38, NFAT5, SGK1, and TCF-1. These findings highlight the functional role of sodium chloride in iNKT cell-mediated inflammatory diseases.
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http://dx.doi.org/10.1002/JLB.3A0217-076RDOI Listing
January 2018

GM-CSF and IL-4 produced by NKT cells inversely regulate IL-1β production by macrophages.

Immunol Lett 2017 02 4;182:50-56. Epub 2017 Jan 4.

Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea; Laboratory of Immune Regulation in Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea; Ischemic/Hypoxia Institute, Seoul National University College of Medicine, Seoul, Republic of Korea. Electronic address:

Natural Killer T (NKT) cells are distinct T cell subset that link innate and adaptive immune responses. IL-1β, produced by various immune cells, plays a key role in the regulation of innate immunity in vivo. However, it is unclear whether NKT cells regulate IL-1β production by macrophages. To address this, we co-cultured NKT cells and peritoneal macrophages in the presence of TCR stimulation and inflammasome activators. Among cytokines secreted from NKT cells, GM-CSF enhanced IL-1β production by macrophages via regulating LPS-mediated pro-IL-1β expression and NLRP3-dependent inflammasome activation, whereas IL-4 enhanced M2-differentiation of macrophages and decreased IL-1β production. Together, our findings suggest the NKT cells have double-sided effects on IL-1β-mediated innate immune responses by producing IL-4 and GM-CSF. These findings may be helpful for a comprehensive understanding of NKT cell-mediated regulatory mechanisms of the pro-inflammatory effects of IL-1β in inflammatory diseases in vivo.
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http://dx.doi.org/10.1016/j.imlet.2017.01.003DOI Listing
February 2017

The roles of innate lymphoid cells in the development of asthma.

Immune Netw 2014 Aug 22;14(4):171-81. Epub 2014 Aug 22.

Department of Medical Science, Seoul National University College of Medicine and Hospital, Seoul 110-744, Korea.

Asthma is a common pulmonary disease with several different forms. The most studied form of asthma is the allergic form, which is mainly related to the function of Th2 cells and their production of cytokines (IL-4, IL-5, and IL-13) in association with allergen sensitization and adaptive immunity. Recently, there have been many advances in understanding non-allergic asthma, which seems to be related to environmental factors such as air pollution, infection, or even obesity. Cells of the innate immune system, including macrophages, neutrophils, and natural killer T cells as well as the newly described innate lymphoid cells, are effective producers of a variety of cytokines and seem to play important roles in the development of non-allergic asthma. In this review, we focus on recent findings regarding innate lymphoid cells and their roles in asthma.
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http://dx.doi.org/10.4110/in.2014.14.4.171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4148487PMC
August 2014
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