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author:("Wang, puue")
1.  Treatment of allergic inflammation and hyperresponsiveness by a simple compound, Bavachinin, isolated from Chinese herbs 
Cellular and Molecular Immunology  2013;10(6):497-505.
Asthmatic inflammation is mediated by a type 2 helper T cell (Th2) cytokine response, and blocking Th2 cytokine production is proven to have a potent therapeutic effect against asthmatic inflammation. Using IL-4-green fluorescent protein (GFP) reporter mice, we demonstrated that Bavachinin, a single compound isolated from a Chinese herb, significantly inhibited Th2 cytokine production, including IL-4, IL-5 and IL-13. Notably, this compound almost completely blocked inflammation in the ovalbumin (OVA)-sensitized animal asthma model. Furthermore, we demonstrated that this chemical selectively affects the level of GATA-3, most likely by affecting the stability of GATA-3 mRNA. Our results demonstrate, for the first time, the potential therapeutic value of this single compound derived from Chinese herbs.
PMCID: PMC4002389  PMID: 24013845
asthma; bavachinin; IL-4
2.  Naturally Activated Vγ4 γδ T Cells Play a Protective Role in Tumor Immunity Through Expression of Eomesodermin1 
Journal of immunology (Baltimore, Md. : 1950)  2010;185(1):10.4049/jimmunol.0903767.
We previously demonstrated that γδ T cells played an important role in tumor immune surveillance by providing an early source of IFN-γ. The precise role of different subsets of γδ T cells in the antitumor immune response, however, is unknown. Vγ1 and Vγ4 γδ T cells are the principal subsets of peripheral lymphoid γδ T cells and they might play distinct roles in tumor immunity. In support of this, we observed that reconstitution of TCRδ−/− mice with Vγ4, but not Vγ1, γδ T cells restored the antitumor response. We also found that these effects were exerted by the activated (CD44high) portion of Vγ4 γδ T cells. We further determined that IFN-γ and perforin are critical elements in the Vγ4-mediated antitumor immune response. Indeed, CD44high Vγ4 γδ T cells produced significantly more IFN-γ and perforin on activation, and showed greater cytolytic activity than did CD44high Vγ1 γδ T cells, apparently due to the high level of eomesodermin (Eomes) in these activated Vγ4 γδ T cells. Consistently, transfection of dominant-negative Eomes in Vγ4 γδ T cells diminished the level of IFN-γ secretion, indicating a critical role of Eomes in the effector function of these γδ T cells. Our results thus reveal distinct functions of Vγ4 and Vγ1 γδ T cells in antitumor immune response, and identify a protective role of activated Vγ4 γδ T cells, with possible implications for tumor immune therapy.
PMCID: PMC3813958  PMID: 20525896
3.  Exo-endocytic trafficking and the septin-based diffusion barrier are required for the maintenance of Cdc42p polarization during budding yeast asymmetric growth 
Molecular Biology of the Cell  2011;22(5):624-633.
The small GTPase Cdc42p is a master regulator of cell polarity. We analyzed Cdc42p localization using yeast mutants and found that endo-exocytic trafficking and septin-based diffusion barrier synergistically control Cdc42p polarization during asymmetric cell growth.
Cdc42p plays a central role in asymmetric cell growth in yeast by controlling actin organization and vesicular trafficking. However, how Cdc42p is maintained specifically at the daughter cell plasma membrane during asymmetric cell growth is unclear. We have analyzed Cdc42p localization in yeast mutants defective in various stages of membrane trafficking by fluorescence microscopy and biochemical fractionation. We found that two separate exocytic pathways mediate Cdc42p delivery to the daughter cell. Defects in one of these pathways result in Cdc42p being rerouted through the other. In particular, the pathway involving trafficking through endosomes may couple Cdc42p endocytosis from, and subsequent redelivery to, the plasma membrane to maintain Cdc42p polarization at the daughter cell. Although the endo-exocytotic coupling is necessary for Cdc42p polarization, it is not sufficient to prevent the lateral diffusion of Cdc42p along the cell cortex. A barrier function conferred by septins is required to counteract the dispersal of Cdc42p and maintain its localization in the daughter cell but has no effect on the initial polarization of Cdc42p at the presumptive budding site before symmetry breaking. Collectively, membrane trafficking and septins function synergistically to maintain the dynamic polarization of Cdc42p during asymmetric growth in yeast.
PMCID: PMC3046059  PMID: 21209323
4.  Current progress in γδ T-cell biology 
T lymphocytes bearing γ- and δ-chain T-cell receptor heterodimers are named γδ T cells. Interestingly, γδ and αβ T cells share the same progenitors, and they undergo a fate decision in the thymus. Functional differentiation of γδ T cells occurs both inside and outside the thymus. Antigen recognition of γδ T-cell receptors is very unique, and the responses frequently exhibit innate characteristics. Nevertheless, peripheral γδ T cells exert a number of effector and regulatory functions. γδ T cells rapidly produce cytokines like interferon (IFN)-γ and IL-17 and promote inflammation, partly due to the inherent epigenetic and transcriptional programs, which facilitates a quick and extensive response. Moreover, γδ T cells lyse target cells directly, and this is necessary for pathogen or tumor clearance. γδ T cells can even serve as regulatory cells, and may contribute to immune suppression. Orchestration of γδ T-cell and other immune cell interactions may be critical for host defense and immune regulation. Recently, γδ T cells have been used for immunotherapy for infectious diseases and malignancy. In this review, we summarize the abstracts presented at the recent γδ T cell Conference held from 19 to 21 May 2010, in Kiel, Germany (please see the website for details:
PMCID: PMC4002965  PMID: 21042298
γδ T cells; immunotherapy; innate immunity
5.  Lethal giant larvae proteins interact with the exocyst complex and are involved in polarized exocytosis 
The Journal of Cell Biology  2005;170(2):273-283.
The tumor suppressor lethal giant larvae (Lgl) plays a critical role in epithelial cell polarization. However, the molecular mechanism by which Lgl carries out its functions is unclear. In this study, we report that the yeast Lgl proteins Sro7p and Sro77p directly interact with Exo84p, which is a component of the exocyst complex that is essential for targeting vesicles to specific sites of the plasma membrane for exocytosis, and that this interaction is important for post-Golgi secretion. Genetic analyses demonstrate a molecular pathway from Rab and Rho GTPases through the exocyst and Lgl to SNAREs, which mediate membrane fusion. We also found that overexpression of Lgl and t-SNARE proteins not only improves exocytosis but also rescues polarity defects in exocyst mutants. We propose that, although Lgl is broadly distributed in the cells, its localized interaction with the exocyst and kinetic activation are important for the establishment and reenforcement of cell polarity.
PMCID: PMC2171422  PMID: 16027223

Results 1-5 (5)