Lab of Immunology & Vaccine Innovation

Research interest

Pathogenic role of CD1 & CD1-reactive T cells in mucosal tissues

Epigenetic regulation of helicase-X

in development and differentiation of iNKT cells

Regulatory Mechanism of

TF-X in CD4 T cell Differentiation and Function

Crosstalk between post-translational modification in immune cells

Pathogenic role of CD1 & CD1-reactive T cells in mucosal tissues

CD1 molecules (CD1a, CD1b, CD1c, and CD1d) are MHC class I-like antigen-presenting molecules that present lipid-based antigens to T cells, initiating their activation. CD1-reactive T cells recognize both self and foreign lipid antigens, contributing to both innate and adaptive immune responses. Given their broad antigen recognition capacity, CD1-reactive T cells are likely to play critical roles in various immune processes, including host defense, autoimmunity, and inflammation.

Our lab investigates the functions of CD1 molecules and CD1-reactive T cells across diverse mucosal immune environments. Specifically, we aim to elucidate the mechanisms underlying CD1-reactive T cell development in the thymus, identify the lipid ligands presented by CD1 molecules and their biosynthetic pathways, and determine how CD1-expressing cells and CD1-reactive T cells contribute to immune responses in inflammatory disorders, autoimmune diseases, and cancer. By uncovering these mechanisms, our research seeks to provide novel insights into CD1-mediated immunity, ultimately paving the way for innovative immunotherapeutic strategies targeting CD1-related pathways.

Epigenetic regulation of helicase-X

in development and differentiation of iNKT cells

Helicase-X (tentative name), traditionally studied in genetics, has recently garnered attention in immunology. This protein exhibits a unique ability to bind nucleic acids such as RNA and DNA and interact with essential cellular proteins and transcription factors. We hypothesize that Helicase-X could serve as a key genetic regulator within immune cells, influencing their differentiation and activation.

We focus on the potential of Helicase-X to regulate critical genes necessary for immune cell functionality, ensuring proper cellular responses. Beyond genetic regulation, we are exploring its role in epigenetics, including histone marker modulation and enhancer formation, which may determine immune cell lineages and activate key genes. Given its central role in immune cell regulation, Helicase-X could contribute to the pathogenesis of immune-related diseases (e.g. tumor) and serve as a potential therapeutic target. Our work aims to uncover the mechanisms underlying these processes and evaluate the therapeutic implications of targeting Helicase-X.

Regulatory Mechanism of TF-X

in CD4 T cell Differentiation and Function

Transcription factor-X(TF-X, tentative name) has been studied as a regulator of cancer cells or embryonic stem cell growth; however, its functions in the immune system remain largely unexplored. However, based on previous studies suggesting TF-X is involved in the growth of specific cells and the fact that many transcription factors with structural similarities to TF-X are key regulators of immune cell development and function, it can be inferred that TF-X may also contribute to the development and function of immune cells.

Especially, our lab aims to elucidate the roles of TF-X in the differentiation and function of CD4 T cells using in vitro and ex vivo models. Through preliminary experiments, we found that TF-X may act as a negative regulator of activation and differentiation of CD4 T cells. Currently, we investigate the molecular mechanisms of TF-X through epigenetic experimental approaches.

Crosstalk between post-translational modification in immune cells

The activity of transcription factors is tightly regulated by post-translational modifications (PTMs), which modulate protein structure and function to control cell signaling, enzyme activation, protein-protein interactions, and other critical processes.

Our lab investigates the diverse roles of PTMs in shaping transcription factor activity and immune cell function. A key interest of our research is understanding the crosstalk between different PTMs—how one modification influences or is influenced by another within a single protein. Based on this concept, we are exploring the hypothesis that methionine oxidation is functionally linked to other PTM events, thereby contributing to the regulation of TF-X(tentative name) activity. Additionally, we aim to elucidate the interplay between oxidative stress, PTM-mediated transcriptional regulation, and immune-related pathologies. Through these studies, we seek to uncover fundamental mechanisms of immune regulation and identify potential therapeutic targets for immune-mediated diseases.

Resarch interest

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Publication

2024

Shin, S. H., Lee, Y. E., Yoon, H. N., Yuk, C. M., An, J. Y., Seo, M., Yoon, S., Oh, M. S., Shin, S. C., Kim, J. H., Kim, Y. J., Kim, J. C., Kim, S. C., & Jang, M. (2024). An innovative strategy harnessing self-activating CAR-NK cells to mitigate TGF-β1-driven immune suppression. Biomaterials, 314, 122888. Advance online publication.

Lee, S., Song, S. G., Kim, G., Kim, S., Yoo, H. J., Koh, J., Kim, Y. J., Tian, J., Cho, E., Choi, Y. S., Chang, S., Shin, H. M., Jung, K. C., Kim, J. H., Kim, T. M., Jeon, Y. K., Kim, H. Y., Shong, M., Kim, J. H., & Chung, D. H. (2024). CRIF1 deficiency induces FOXP3LOW inflammatory non-suppressive regulatory T cells, thereby promoting antitumor immunity. Science advances, 10(13), eadj9600.

Sharma, P., Zhang, X., Ly, K., Zhang, Y., Hu, Y., Ye, A. Y., Hu, J., Kim, J. H., Lou, M., Wang, C., Celuzza, Q., Kondo, Y., Furukawa, K., Bundle, D. R., Furukawa, K., Alt, F. W., & Winau, F. (2024). The lipid globotriaosylceramide promotes germinal center B cell responses and antiviral immunity. Science (New York, N.Y.), 383(6684), eadg0564.

Sharma, P., Zhang, X., Ly, K., Kim, J. H., Wan, Q., Kim, J., Lou, M., Kain, L., Teyton, L., & Winau, F. (2024). Hyperglycosylation of prosaposin in tumor dendritic cells drives immune escape. Science (New York, N.Y.), 383(6679), 190–200.

2023

Koh, J., Woo, Y. D., Yoo, H. J., Choi, J. P., Kim, S. H., Chang, Y. S., Jung, K. C., Kim, J. H., Jeon, Y. K., Kim, H. Y., & Chung, D. H. (2023). De novo fatty-acid synthesis protects invariant NKT cells from cell death, thereby promoting their homeostasis and pathogenic roles in airway hyperresponsiveness. eLife, 12, RP87536.

Kim, S., Cho, S., & Kim, J. H. (2023). CD1-mediated immune responses in mucosal tissues: molecular mechanisms underlying lipid antigen presentation system. Experimental & molecular medicine, 10.1038/s12276-023-01053-6.

2022

Yoo, H. J., Choi, D. W., Roh, Y. J., Lee, Y. M., Lim, J. H., Eo, S., Lee, H. J., Kim, N. Y., Kim, S., Cho, S., Im, G., Lee, B. C., & Kim, J. H. (2022). MsrB1-regulated GAPDH oxidation plays programmatic roles in shaping metabolic and inflammatory signatures during macrophage activation. Cell reports, 41(6), 111598.

Shin, J. W., Kim, J., Ham, S., Choi, S. M., Lee, C. H., Lee, J. C., Kim, J. H., Cho, S. H., Kang, H. R., Kim, Y. M., Chung, D. H., Chung, Y., Bae, Y. S., Bae, Y. S., Roh, T. Y., Kim, T., & Kim, H. Y. (2022). A unique population of neutrophils generated by air pollutant-induced lung damage exacerbates airway inflammation. The Journal of allergy and clinical immunology, 149(4), 1253–1269.e8.

Nam, S. Y., Lee, J., Shin, S. S., Yoo, H. J., Yun, M., Kim, S., Kim, J. H., Lee. J. (2022). Antibacterial and cytotoxic properties of star-shaped quaternary ammonium-functionalized polymers with different pendant groups. Polymer Chemistry, 13(12), 1763-1773.

Lee, H. M., Choi, D. W., Kim, S., Lee, A., Kim, M., Roh, Y. J., Jo, Y. H., Cho, H. Y., Lee, H. J., Lee, S. R., Tarrago, L., Gladyshev, V. N., Kim, J. H., & Lee, B. C. (2022). Biosensor-Linked Immunosorbent Assay for the Quantification of Methionine Oxidation in Target Proteins. ACS sensors, 7(1), 131–141.

2021

Yoo, H. J., Kim, N. Y., & Kim, J. H. (2021). Current Understanding of the Roles of CD1a-Restricted T Cells in the Immune System. Molecules and cells, 44(5), 310–317.

Kim, J., Shin, J. W., Lee, H. J., Kim, J. H., Choi, S. M., Lee, C. H., Kang, H. R., Park, S. H., Bae, Y. S., Chung, D. H., & Kim, H. Y. (2021). Serum amyloid A promotes emphysema by triggering the reciprocal activation of neutrophils and ILC3s. Clinical and translational medicine, 11(12), e637.

Sun, Z., Kim, J. H., Kim, S. H., Kim, H. R., Zhang, K., Pan, Y., Ko, M. K., Kim, B. M., Chu, H., Lee, H. R., Kim, H. L., Kim, J. H., Fu, X., Hyun, Y. M., Yun, K. N., Kim, J. Y., Lee, D. W., Song, S. Y., Lin, C. P., Clark, R. A., … Park, C. O. (2021). Skin-resident natural killer T cells participate in cutaneous allergic inflammation in atopic dermatitis. The Journal of allergy and clinical immunology, 147(5), 1764–1777.

2020

Kim, G. H., Fang, X. Q., Lim, W. J., Park, J., Kang, T. B., Kim, J. H., & Lim, J. H. (2020). Cinobufagin Suppresses Melanoma Cell Growth by Inhibiting LEF1. International journal of molecular sciences, 21(18), 6706.

Ryu, S., Lee, E. Y., Kim, D. K., Kim, Y. S., Chung, D. H., Kim, J. H., Lee, H., & Kim, H. Y. (2020). Reduction of circulating innate lymphoid cell progenitors results in impaired cytokine production by innate lymphoid cells in patients with lupus nephritis. Arthritis research & therapy, 22(1), 63.

Kim, J. H., Yoon, C. Y., Jun, Y., Lee, B. B., Lee, J. E., Ha, S. D., Woo, H., Choi, A., Lee, S., Jeong, W., Kim, J. H., & Kim, T. (2020). NuA3 HAT antagonizes the Rpd3S and Rpd3L HDACs to optimize mRNA and lncRNA expression dynamics. Nucleic acids research, 48(19), 10753–10767.

Lee, H. J., Park, J. S., Yoo, H. J., Lee, H. M., Lee, B. C., & Kim, J. H. (2020). The Selenoprotein MsrB1 Instructs Dendritic Cells to Induce T-Helper 1 Immune Responses. Antioxidants (Basel, Switzerland), 9(10), 1021.

2019

Kim, G. H., Kan, S. Y., Kang, H., Lee, S., Ko, H. M., Kim, J. H., & Lim, J. H. (2019). Ursolic Acid Suppresses Cholesterol Biosynthesis and Exerts Anti-Cancer Effects in Hepatocellular Carcinoma Cells. International journal of molecular sciences, 20(19), 4767.

Kang, H., Oh, T., Bahk, Y. Y., Kim, G. H., Kan, S. Y., Shin, D. H., Kim, J. H., & Lim, J. H. (2019). HSF1 Regulates Mevalonate and Cholesterol Biosynthesis Pathways. Cancers, 11(9), 1363.

Lee, Y. M., Kim, G. H., Park, E. J., Oh, T. I., Lee, S., Kan, S. Y., Kang, H., Kim, B. M., Kim, J. H., & Lim, J. H. (2019). Thymoquinone Selectively Kills Hypoxic Renal Cancer Cells by Suppressing HIF-1α-Mediated Glycolysis. International journal of molecular sciences, 20(5), 1092.

2018

Park, J. S., & Kim, J. H. (2018). Role of non-classical T cells in skin immunity. Molecular immunology, 103, 286–292.

Kim, Y. S., Lee, Y. M., Oh, T. I., Shin, D. H., Kim, G. H., Kan, S. Y., Kang, H., Kim, J. H., Kim, B. M., Yim, W. J., & Lim, J. H. (2018). Emodin Sensitizes Hepatocellular Carcinoma Cells to the Anti-Cancer Effect of Sorafenib through Suppression of Cholesterol Metabolism. International journal of molecular sciences, 19(10), 3127.

Ryu, S., Park, J. S., Kim, H. Y., & Kim, J. H. (2018). Lipid-Reactive T Cells in Immunological Disorders of the Lung. Frontiers in immunology, 9, 2205.

2011 ~ 2017

Lee, B. C., Lee, S. G., Choo, M. K., Kim, J. H., Lee, H. M., Kim, S., Fomenko, D. E., Kim, H. Y., Park, J. M., & Gladyshev, V. N. (2017). Selenoprotein MsrB1 promotes anti-inflammatory cytokine gene expression in macrophages and controls immune response in vivo. Scientific reports, 7(1), 5119.

Beyaz, S., Kim, J. H., Pinello, L., Xifaras, M. E., Hu, Y., Huang, J., Kerenyi, M. A., Das, P. P., Barnitz, R. A., Herault, A., Dogum, R., Haining, W. N., Yilmaz, Ö. H., Passegue, E., Yuan, G. C., Orkin, S. H., & Winau, F. (2017). The histone demethylase UTX regulates the lineage-specific epigenetic program of invariant natural killer T cells. Nature immunology, 18(2), 184–195.

Hu, Y., Kim, J. H., He, K., Wan, Q., Kim, J., Flach, M., Kirchhausen, T., Vortkamp, A., & Winau, F. (2016). Scramblase TMEM16F terminates T cell receptor signaling to restrict T cell exhaustion. The Journal of experimental medicine, 213(12), 2759–2772.

Kim, J. H., Hu, Y., Yongqing, T., Kim, J., Hughes, V. A., Le Nours, J., Marquez, E. A., Purcell, A. W., Wan, Q., Sugita, M., Rossjohn, J., & Winau, F. (2016). CD1a on Langerhans cells controls inflammatory skin disease. Nature immunology, 17(10), 1159–1166.

Oh, S. J., Ahn, S., Jin, Y. H., Ishifune, C., Kim, J. H., Yasutomo, K., & Chung, D. H. (2015). Notch 1 and Notch 2 synergistically regulate the differentiation and function of invariant NKT cells. Journal of leukocyte biology, 98(5), 781–789.

Kim, J., Kim, J. H., & Winau, F. (2014). Thinking inside the box: endogenous α-anomeric lipid antigens. Immunity, 41(4), 505–506.

Kim, J. H., Oh, S. J., Ahn, S., & Chung, D. H. (2014). IFN-γ-producing NKT cells exacerbate sepsis by enhancing C5a generation via IL-10-mediated inhibition of CD55 expression on neutrophils. European journal of immunology, 44(7), 2025–2035.

Oh, S. J., Kim, J. H., & Chung, D. H. (2013). NOD2-mediated suppression of CD55 on neutrophils enhances C5a generation during polymicrobial sepsis. PLoS pathogens, 9(5), e1003351.

Kim, J. H., Kim, H. S., Kim, H. Y., Oh, S. J., & Chung, D. H. (2012). Direct engagement of TLR4 in invariant NKT cells regulates immune diseases by differential IL-4 and IFN-γ production in mice. PloS one, 7(9), e45348.

Kim, J. H., & Chung, D. H. (2011). CD1d-restricted IFN-γ-secreting NKT cells promote immune complex-induced acute lung injury by regulating macrophage-inflammatory protein-1α production and activation of macrophages and dendritic cells. Journal of immunology (Baltimore, Md. : 1950), 186(3), 1432–1441.

2004 ~ 2010

Hwang, S. J., Kim, J. H., Kim, H. Y., Kim, S., & Chung, D. H. (2010). FTY720, a sphingosine 1-phosphate receptor modulator, inhibits CD1d-restricted NKT cells by suppressing cytokine production but not migration. Laboratory investigation; a journal of technical methods and pathology, 90(1), 9–19.

Oh, S. J., Kim, J. H., Min, C. K., & Chung, D. H. (2008). Role of type II NKT cells in the suppression of graft-versus-host disease. Critical reviews in immunology, 28(3), 249–267.

Kim, J. H., Choi, E. Y., & Chung, D. H. (2007). Donor bone marrow type II (non-Valpha14Jalpha18 CD1d-restricted) NKT cells suppress graft-versus-host disease by producing IFN-gamma and IL-4. Journal of immunology (Baltimore, Md. : 1950), 179(10), 6579–6587.

Kim, J. H., Kim, H. Y., Kim, S., Chung, J. H., Park, W. S., & Chung, D. H. (2005). Natural killer T (NKT) cells attenuate bleomycin-induced pulmonary fibrosis by producing interferon-gamma. The American journal of pathology, 167(5), 1231–1241.