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Full-Text Articles in Medicine and Health Sciences
Differential Regulation Of Osteoblast Activity By Th Cell Subsets Mediated By Parathyroid Hormone And Ifn-, Nathan Young, Natallia Mikhalkevich, Ying Yan, Di Chen, Wei-Ping Zeng
Differential Regulation Of Osteoblast Activity By Th Cell Subsets Mediated By Parathyroid Hormone And Ifn-, Nathan Young, Natallia Mikhalkevich, Ying Yan, Di Chen, Wei-Ping Zeng
Wei-ping Zeng
Bone loss is a typical pathological feature of chronic inflammatory bone diseases including rheumatoid arthritis, in which CD4 effector T cells play critical roles. We found that activated mouse Th2 and not Th1 cells produced the parathyroid hormone (PTH). Unlike in the parathyroid cells, PTH expression in Th2 cells was not regulated by the fluctuation of calcium level, but rather it required the full activation of the T cells. Although PTH was expressed in immature Th2 cells, and its receptor was transiently expressed during Th1 and Th2 cell differentiation, PTH did not significantly affect the outcome of the differentiation. In …
Susceptibility To Autoimmunity And B Cell Resistance To Apoptosis In Mice Lacking Androgen Receptor In B Cells, Saleh Altuwaijri, Kuang-Hsiang Chuang, Kuo-Pao Lai, Jiann-Jyh Lai, Hung-Yun Lin, Faith Young, Andrea Bottaro, Meng-Yin Tsai, Wei-Ping Zeng, Hong-Chiang Chang, Shuyuan Yeh, Chawnshang Chang
Susceptibility To Autoimmunity And B Cell Resistance To Apoptosis In Mice Lacking Androgen Receptor In B Cells, Saleh Altuwaijri, Kuang-Hsiang Chuang, Kuo-Pao Lai, Jiann-Jyh Lai, Hung-Yun Lin, Faith Young, Andrea Bottaro, Meng-Yin Tsai, Wei-Ping Zeng, Hong-Chiang Chang, Shuyuan Yeh, Chawnshang Chang
Wei-ping Zeng
Estrogens have been linked to a higher female incidence of autoimmune diseases. The role of androgen and the androgen receptor (AR) in autoimmune diseases, however, remains unclear. Here we report that the lack of AR in B cells in different strains of mice, namely general AR knockout, B cell-specific AR knockout, and naturally occurring testicular feminization mutation AR-mutant mice, as well as castrated wild-type mice, results in increased B cells in blood and bone marrow. Analysis of the targeted mice, together with bone marrow transplantation using Rag1 recipients, overexpression of retrovirally encoded AR-cDNA, and small interfering RNA-mediated AR mRNA knockdown …
Domain Requirements For The Diverse Immune Regulatory Functions Of Foxp3, Wei-Ping Zeng, Vincent E. Sollars, Andrea Del Pilar Belalcazar
Domain Requirements For The Diverse Immune Regulatory Functions Of Foxp3, Wei-Ping Zeng, Vincent E. Sollars, Andrea Del Pilar Belalcazar
Wei-ping Zeng
Foxp3 is responsible for the major immunological features of Treg cells, including hypoproliferation in vitro, immune suppression of conventional T cells and resistance to Th2 cell differentiation. In addition to the Forkhead domain, the Foxp3 protein contains the N-terminal, zinc finger and leucine zipper domains. To understand how these domains contribute to Foxp3 functions, we systematically compared the roles of these domains in determining the 3 major immunological features of Treg cells. We designed a bridge-mediated mutagenesis method to generate Foxp3 mutants with complete deletion of each of the domains. CD4 T cells expressing the Foxp3 mutant with deletion of …
Responsiveness Of Naive Cd4 T Cells To Polarizing Cytokine Determines The Ratio Of Th1 And Th2 Cell Differentiation, Natallia Mikhalkevich, Brian Becknell, Michael Caligiuri, Michael Bates, Richard Harvey, Wei-Ping Zeng
Responsiveness Of Naive Cd4 T Cells To Polarizing Cytokine Determines The Ratio Of Th1 And Th2 Cell Differentiation, Natallia Mikhalkevich, Brian Becknell, Michael Caligiuri, Michael Bates, Richard Harvey, Wei-Ping Zeng
Wei-ping Zeng
The intrinsic features of naive CD4 T cells that affect their ability to respond to polarizing signals for Th cell differentiation are not well understood. In this study, we show that naive CD4 T cells from mice transgenic for the Hlx gene expressed lower levels of IL-4Rα. The down-regulation of IL-4Rα diminished IL-4 signaling and the Th2 response and enhanced the Th1 response under suboptimal polarizing conditions. In nontransgenic CD4 T cells, blocking IL-4Rα with Abs had the same effect in an Ab dose-dependent manner. Conversely, Hlx haploinsufficiency caused higher expression of IL-4Rα to favor Th2 cell differentiation. Thus, the …
Temporal And Spatial Changes Of Histone 3 K4 Dimethylation At The Ifn-Γ Gene During Th1 And Th2 Cell Differentiation, Heli Hamalainen-Laanaya, James Kobie, Chawnshang Chang, Wei-Ping Zeng
Temporal And Spatial Changes Of Histone 3 K4 Dimethylation At The Ifn-Γ Gene During Th1 And Th2 Cell Differentiation, Heli Hamalainen-Laanaya, James Kobie, Chawnshang Chang, Wei-Ping Zeng
Wei-ping Zeng
Covalent modification of nucleosomal histones is an important mechanism for cytokine gene regulation in Th1 and Th2 cells. In this study, we analyzed the kinetics of histone H3 K4 dimethylation (H3K4me2) of the IFN-γ gene. Minimal levels of H3K4me2 were found in naive CD4 T cells. After 5 days of differentiation, H3K4me2 levels were elevated in both Th1 and Th2 cells at the −5.3 kb, the promoter, the intronic DNase I hypersensitive sites, and 3′ distal sites including the +9.5 kb and +16 kb sites. Th1 cells maintained high levels of H3K4me2 after longer time of culture. However, in Th2 …
Up-Regulation Of Hlx In Immature Th Cells Induces Ifn-Γ Expression, Wei-Ping Zeng, Qian Zhao, Xinyan Zhao, Baiyong Li, Mike Hubank, David Schatz, Richard Flavell
Up-Regulation Of Hlx In Immature Th Cells Induces Ifn-Γ Expression, Wei-Ping Zeng, Qian Zhao, Xinyan Zhao, Baiyong Li, Mike Hubank, David Schatz, Richard Flavell
Wei-ping Zeng
Differentiation of Th cells from naive precursors is a dynamic process that involves multiple transcription factors acting at specific time points to regulate gene expression. In this study we show that the homeobox transcription factor Hlx is up-regulated early in Th1 cell differentiation. Mice constitutively expressing an Hlx transgene driven by a CD4 promoter showed marked reduction in the CD4+CD8+ thymocyte population. The Hlx transgenic mice generated increased numbers of Th1 cells in response to keyhole limpet hemocyanin immunization. After differentiation under Th2-polarizing conditions in vitro, the transgenic CD4 T cells expressed high levels of IFN-γ. Intracellular …
Interaction Between Gata-3 And The Transcriptional Coregulator Pias1 Is Important For The Regulation Of Th2 Immune Responses, Xinyan Zhao, Bo Zheng, Yanfang Huang, Dan Yang, Shoshana Katzman, Chawnshang Chang, Deborah Fowell, Wei-Ping Zeng
Interaction Between Gata-3 And The Transcriptional Coregulator Pias1 Is Important For The Regulation Of Th2 Immune Responses, Xinyan Zhao, Bo Zheng, Yanfang Huang, Dan Yang, Shoshana Katzman, Chawnshang Chang, Deborah Fowell, Wei-Ping Zeng
Wei-ping Zeng
Th2 cytokine expression is dependent on the transcription factor GATA-3. However, the molecular interactions of GATA-3 leading to Th2 cytokine gene activation have not been well characterized. Here, we reported a number of GATA-3 associated proteins in Th2 cells, and one of such proteins Pias1 functioned as a positive transcriptional coregulator for GATA-3. When overexpressed in Th2 cells, Pias1 enhanced the expression of IL-13, and to lesser degrees, IL-4 and -5. Conversely, Pias1 siRNA down-regulated the Th2 cytokine expression. In Leishmania major infection, manipulating Pias1 expression in parasite-reactive CD4 T cells altered severity of disease caused by Th2 responses. Mechanistically, …