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 (gc) cytokine receptor that is responsible for the severity of inflammatory autoimmune disease. His current research is primarily focused on the effect of gc cytokine receptor expression and regulation on T cell activation and differentiation.
A. The role of cytokines in immune cell homeostasis under resting and immune activating conditions. Different cell populations occupy different niches for homeostasis. Hence, naive and memory T cells don't compete with each other for limiting resources such as pro-survival cytokines. Whether such niches are privileged sites even to immune activated cells is not clear. In fact, how naive and memory T cell homeostasis works under disease conditions, where large numbers of cells are activated and proliferating, remains to be unraveled. In a previous study (Immunity (2004) 21:289-302), we showed that inflammatory cytokines such as IL-2, IL-4 and IL-6 suppress the transcription and expression of IL-7 receptors. Furthermore, we predicted that such a mechanism would downregulate IL-7 receptor expression on activated T cells thus effectively removing them from the naive T cell pool and out of competition for IL-7-mediated survival signals. However, whether and how such T cell homeostasis is achieved is largely not known. In this regard, we are interested in investigating the underlying mechanism of homeostasis under immune activation circumstances, and we are approaching this issue by analyzing the survival and functional/phenotypic changes of both nave and memory T cells in tumor bearing animals and in different inflammatory models. Analyzing animals transgenic for specific survival cytokine receptors is another important part of our studies that will provide further clues on the role of cytokines in regulating homeostasis. We anticipate that using such animals in combination with cancer or inflammatory models will open new doors for understanding T cell homeostasis in diseases.
B. Regulatory mechanism of cytokine receptor expression and signaling during immune cell homeostasis and activation. Cytokine receptor expression is dynamically regulated during development and activation of the immune system. IL-7 downregulates transcription and expression of its own receptor, while other gamma c-chain cytokines such as IL-2 and IL-4 upregulate expression of their own receptors. We are investigating the biological implications of such distinct cytokine receptor regulation, in particular, with a focus on T cell homeostasis.
Additionally, we are interested in the molecular mechanisms and intracellular signaling pathways that govern cytokine receptor expression. Most recently, we identified a novel nuclear factor involved in IL-7R transcription, and we confirmed its regulatory role in vivo. Investigations on the mechanism how such factors are regulated and how they affect T cell function is another major research topic of our lab.
Activated T cells secrete an alternatively spliced form of common γ-chain that inhibits cytokine signaling and exacerbates inflammation.Immunity. 40: 910-23, 2014. [ Journal Article ]
The transcription factor ThPOK suppresses Runx3 and imposes CD4(+) lineage fate by inducing the SOCS suppressors of cytokine signaling.Nat. Immunol. 15: 638-45, 2014. [ Journal Article ]
Ikaros is required to survive positive selection and to maintain clonal diversity during T cell development in the thymus.Blood. 122: 2358-68, 2013. [ Journal Article ]
Pim1 permits generation and survival of CD4(+) T cells in the absence of γc cytokine receptor signaling.Eur. J. Immunol. 43: 2283-94, 2013. [ Journal Article ]
- J. Immunol. 188: 5859-66, 2012. [ Journal Article ]
Dr. Park received his Ph.D. from the Julius-Maximilians University in Wurzburg, Germany. After obtaining postdoctoral training at the Korea Research Institute of Bioscience and Biotechnology in South Korea, he joined the NCI-CCR's Experimental Immunology Branch as a research fellow where he studied the role of IL-7 signaling in T cell development and homeostasis. Since 2008, Dr. Park has been a tenure-track investigator at the Experimental Immunology Branch where he is investigating the mechanisms of cytokine receptor regulation and signaling in immune cells.
|Megan Davis||Research Biologist|
|Devon Dipalma||Postbaccalaureate Fellow (CRTA)|
|Sujin Hwang||Postdoctoral Fellow (CRTA)|
|Davinna Ligons Ph.D.||Postdoctoral Fellow (CRTA)|
|Joo Young Park D.D.S., Ph.D.||Postdoctoral Fellow (Visiting)|
|Adam Waickman Ph.D.||Postdoctoral Fellow (CRTA)|