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Jung-Hyun  Park, Ph.D.

Jung-Hyun Park, Ph.D.

  • Center for Cancer Research
  • National Cancer Institute
Experimental Immunology Branch

RESEARCH SUMMARY

Dr. Park has a long standing interest in cytokines and their roles in T cell development and differentiation. He reported a role for intra-thymic cytokines in T cell lineage choice and maturation, and he also identified a new mechanism of peripheral T cell homeostasis that is mediated by cytokine-induced tuning of coreceptor expression. Recently, he reported identification of a soluble form of the common gamma-chain (γc) cytokine receptor that is responsible for the severity of inflammatory autoimmune disease. His current research is primarily focused on the effect of γc cytokine receptor expression and regulation on T cell activation and differentiation.

Areas of Expertise

1) cytokine receptor expression, 2) cytokine signaling, 3) T cell development, 4) T cell differentiation, 5) thymus, 6) inflammation

Publications

Selected Recent Publications

In vivo availability of the cytokine IL-7 constrains the survival and homeostasis of peripheral iNKT cells

Joo-Young Park, Hee Yeun Won, Devon T DiPalma, Hye Kyung Kim, Tae-Hyoun Kim, Can Li, Noriko Sato, Changwan Hong, Ninan Abraham, Ronald E Gress, Jung-Hyun Park
Cell Rep.. 38(2): 110219, 2022.
Full-Text Article
[ Journal Article ]

Quantitative Difference in PLZF Protein Expression Determines iNKT Lineage Fate and Controls Innate CD8 T Cell Generation

Park JY, DiPalma DT, Kwon J, Fink J, Park JH.
Cell Rep. 27(9): 2548-2557.e4, 2019. [ Journal Article ]

RORγt limits the amount of the cytokine receptor γc through the prosurvival factor Bcl-x(L) in developing thymocytes

Ligons DL, Hwang S, Waickman AT, Park JY, Luckey MA, Park JH.
Sci Signal. 11(545): pii: eaam8939, 2018. [ Journal Article ]

Activated T cells secrete an alternatively spliced form of common γ-chain that inhibits cytokine signaling and exacerbates inflammation

Hong C, Luckey MA, Ligons DL, Waickman AT, Park JY, Kim GY, Keller HR, Etzensperger R, Tai X, Lazarevic V, Feigenbaum L, Catalfamo M, Walsh ST, Park JH.
Immunity. 40(6): 910-23, 2014. [ Journal Article ]

The transcription factor ThPOK suppresses Runx3 and imposes CD4(+) lineage fate by inducing the SOCS suppressors of cytokine signaling

Luckey MA, Kimura MY, Waickman AT, Feigenbaum L, Singer A, Park JH.
Nat. Immunol. 15(7): 638-45, 2014. [ Journal Article ]

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Covers

Science Signaling cover - August 28, Vol. 11, Issue 545, 2018

RORγt limits the amount of the cytokine receptor γc through the prosurvival factor Bcl-x(L) in developing thymocytes

Published Date

About the Cover: The cover image shows an electron micrograph of a double-positive thymocyte from an RORγt-deficient, Bcl-x(L) transgenic mouse

The cytokine receptor subunit γc provides critical signals for T cell survival and differentiation. We investigated the molecular mechanism that controls the cell surface abundance of γc during T cell development in the thymus. We found that the amount of γc was low on CD4+CD8+ double-positive (DP) thymocytes before their positive selection to become mature T cells. The transcription factor RORγt was abundant in immature DP thymocytes, and its loss resulted in an increase in the abundance of surface γc, specifically on preselection DP cells. Rather than directly repressing expression of the gene encoding γc, RORγt acted through the antiapoptotic protein Bcl-xL to reduce the abundance of surface γc, which resulted in decreased cytokine signaling and was associated with inhibition of cell metabolism and mitochondrial biogenesis. Accordingly, overexpression of Bcl-xL in RORγt-deficient thymocytes restored the amount of surface γc to that present on normal preselection DP cells. Together, these data highlight a previously unappreciated role for RORγt and Bcl-xL in limiting γc abundance at the cell surface and reveal a signaling circuit in which survival factors control cytokine signaling by limiting the abundance and surface distribution of a receptor subunit shared by several cytokines.

Citation

RORγt limits the amount of the cytokine receptor γc through the prosurvival factor Bcl-x(L) in developing thymocytes. Ligons DL, Hwang S, Waickman AT, Park JY, Luckey MA, Park JH. Sci Signal. 2018 Aug 28;11(545), pii: eaam8939. doi: 10.1126/scisignal.aam8939.