- April 1-6, 2011 - Keystone Symposia Scholarship - Travel Award
Keystone Symposia -- Immunoregulatory Networks Conference in Colorado
Yu-Hui Huang attended National Taiwan University in Taiwan from 1997 to 2001, and graduated with a Bachelor of Horticultural Sciences degree in 2001. She next continued to pursue a Masters degree of Biopharmaceutical Sciences in National Yang-Ming University in Taiwan under the guidance of professor Rong-Tsun Wu from 2001 to 2003, and received a Master of Science degree in 2003. Thereafter, she worked as a research assistant in National Taiwan University Hospital from 2003 to 2005, followed by working as a research technician in Washington University in St. Louis in USA from 2005 to 2006. In the Fall of 2006, she came to the University of Rochester in USA and began graduate studies in the Department of Microbiology and Immunology. She earned the Keystone Symposia Scholarship in 2011. She pursued her research on the control of T cell receptor signaling by natural regulatory T cells under the guidance of professor Deborah Fowell, and received the Masters of Science degree from the University of Rochester in 2004.
Nature Regulatory T cells (nTregs) have functions that inhibit the activation of T and B lymphocytes and innate cells. Their suppressive function is critical in maintaining peripheral tolerance. Failure to control unnecessary immune activation results in autoimmunity. In 1998 nTregs were reported to inhibit conventional CD4 T cell proliferation by suppressing IL-2, a T cell growth factor. However the mechanisms of IL-2 inhibition are still unknown. Production of IL-2 requires T cell receptor (TCR) engagement that leads to nuclear translocation of transcription factors NFAT, NFkB, and AP-1. We hypothesized that nTregs inhibit IL-2 through modulation of TCR signaling. To test our hypothesis, we used ImageStream to measure nuclear localization of transcription factors. ImageStream is a novel flow-based technology that allows us to visualize nuclear localization at the single cell level and generate robust data for statistical analysis. We asked if nTregs alter the nuclear localization of transcription factors in target CD4 T cells. We found that Tregs did not change the nuclear localization of NFAT1, NFAT2, or AP-1 components c-Fos and c-Jun. Rather, nTregs specifically attenuated the nuclear localization of p65, a NFkB subunit. This result implies that nTregs do not globally terminate TCR signaling but selectively inhibit signaling required for p65 nuclear localization. Mechanistically, we demonstrated that Treg inhibition of IL-2 and p65 requires close proximity, and is independent of antigen-presenting cells. This result suggests a potential T-T interaction might occur. One possibility to achieve suppression would be to induce intrinsic negative regulators in target CD4 cells but analysis of cAMP and E3 ligases failed to identify regulatory elements. However, addition of a strong stimulus from CD28 abrogated Treg suppression of p65. Thus, in the steady state, Tregs may dampen p65 signals to avoid activation of self-reactive cells, a mechanisms that can be overridden in response to infection via provision of co-stimulatory signals. Future experiments are needed to determine how nTregs specifically inhibit p65 without disturbing the signals required for NFAT and AP-1. Understanding this mechanism will be critical to know how nTregs work and help with therapeutic strategies for autoimmunity or cancer.
- Yu-Hui Huang, Dorothy K. Sojka and Deborah J. Fowell. 2012. Cutting Edge: Regulatory T cells selectively attenuate, not terminate, T cell signaling by disrupting NFκB nuclear accumulation in CD4 T cells. Journal of Immunology, 188:947-951.
- Dorothy K Sojka, Christopher A Lazarski, Yu-Hui Huang, Irina Bromberg, Angela Hughson, Deborah J Fowell. Regulation of immunity at tissue sites of inflammation. 2009. Immunologic Research 45(2-3): 239-250.
- Dorothy K. Sojka, Yu-Hui Huang, and Deborah J. Fowell. Mechanisms of regulatory T-cell suppression – a diverse arsenal for a moving target. 2008. Immunology 124, 13-22.
- Yao-Hsu Yang, Yu-Hui Huang, Yu-Li Lin, Li-Chieh Wang, Ya-Hui Chuang, Yu-Tsan Lin, Bor-Luen Chiang. Circulating IgA from acute stage of childhood Henoch-Schönlein purpura can enhance endothelial interleukin (IL)-8 production through MEK/ERK signalling pathway. 2006. Clinical and Experimental Immunology, 144, 247-253.
- Yao-Hsu Yang, Yu-Hui Huang, Ya-Hui Chuang, Chung-Min Peng, Li-Chieh Wang, Yu-Tsan Lin, Bor-Luen Chiang. Autoantibodies against Human Epithelial Cells and Endothelial Cells after Severe Acute Respiratory Syndrome (SARS)-Associated Coronavirus Infection. 2005. Journal of Medical Virology, 77(1): 1-7.