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Full-Text Articles in Medicine and Health Sciences
Regulation Of Ifn-Γ Expression, John Fenimore, Howard A. Young
Regulation Of Ifn-Γ Expression, John Fenimore, Howard A. Young
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Interferon gamma, referred to here as IFN- γ, is a major component in immunological cell signaling and is a critical regulatory protein for overall immune system function. First discovered in 1965 (Wheelock Science 149: (3681)310–311, 1965), IFN- γ is the only Type II interferon identified. Its expression is both positively and negatively controlled by different factors. In this chapter, we will review the transcriptional and post-transcriptional control of IFN-γ expression. In the transcriptional control part, the regular activators and suppressors are summarized, we will also focus on the epigenetic control, such as chromosome access, DNA methylation, and histone acetylation. The …
Chronic Expression Of Interferon-Gamma Leads To Murine Autoimmune Cholangitis With A Female Predominance, Heekyong R. Bae, Patrick S.C. Leung, Koichi Tsuneyama, Julio C. Valencia, Deborah L. Hodge, Seohyun Kim, Tim Back, Megan Karwan, Anand S. Merchant, Nobuyuki Baba, Dechun Feng, Ogyi Park, Bin Gao, Guo Xiang Yang, M. Eric Gershwin, Howard A. Young
Chronic Expression Of Interferon-Gamma Leads To Murine Autoimmune Cholangitis With A Female Predominance, Heekyong R. Bae, Patrick S.C. Leung, Koichi Tsuneyama, Julio C. Valencia, Deborah L. Hodge, Seohyun Kim, Tim Back, Megan Karwan, Anand S. Merchant, Nobuyuki Baba, Dechun Feng, Ogyi Park, Bin Gao, Guo Xiang Yang, M. Eric Gershwin, Howard A. Young
Public Health Resources
In most autoimmune diseases the serologic hallmarks of disease precede clinical pathology by years. Therefore, the use of animal models in defining early disease events becomes critical. We took advantage of a “designer” mouse with dysregulation of interferon gamma (IFNγ) characterized by prolonged and chronic expression of IFNγ through deletion of the IFNγ 3′-untranslated region adenylate uridylate-rich element (ARE). The ARE-Del-/- mice develop primary biliary cholangitis (PBC) with a female predominance that mimics human PBC that is characterized by up-regulation of total bile acids, spontaneous production of anti-mitochondrial antibodies, and portal duct inflammation. Transfer of CD4 T cells from ARE-Del-/- …
Cd4 T Cell-Derived Ifn-Γ Plays A Minimal Role In Control Of Pulmonary Mycobacterium Tuberculosis Infection And Must Be Actively Repressed By Pd-1 To Prevent Lethal Disease, Shunsuke Sakai, Keith D. Kauffman, Michelle A. Sallin, Arlene H. Sharpe, Howard A. Young, Vitaly V. Ganusov, Daniel L. Barber
Cd4 T Cell-Derived Ifn-Γ Plays A Minimal Role In Control Of Pulmonary Mycobacterium Tuberculosis Infection And Must Be Actively Repressed By Pd-1 To Prevent Lethal Disease, Shunsuke Sakai, Keith D. Kauffman, Michelle A. Sallin, Arlene H. Sharpe, Howard A. Young, Vitaly V. Ganusov, Daniel L. Barber
Public Health Resources
IFN-γ–producing CD4 T cells are required for protection against Mycobacterium tuberculosis (Mtb) infection, but the extent to which IFN-γ contributes to overall CD4 T cell-mediated protection remains unclear. Furthermore, it is not known if increasing IFN-γ production by CD4 T cells is desirable in Mtb infection. Here we show that IFN-γ accounts for only ~30% of CD4 T cell-dependent cumulative bacterial control in the lungs over the first six weeks of infection, but >80% of control in the spleen. Moreover, increasing the IFN-γ–producing capacity of CD4 T cells by ~2 fold exacerbates lung infection and leads to the early death …
Aging Converts Innate B1a Cells Into Potent Cd8+ T Cell Inducers, Catalina Lee-Chang, Monica Bodogai, Kanako Moritoh, Xin Chen, Robert Wersto, Ranjan Sen, Howard A. Young, Michael Croft, Luigi Ferrucci, Arya Biragyn
Aging Converts Innate B1a Cells Into Potent Cd8+ T Cell Inducers, Catalina Lee-Chang, Monica Bodogai, Kanako Moritoh, Xin Chen, Robert Wersto, Ranjan Sen, Howard A. Young, Michael Croft, Luigi Ferrucci, Arya Biragyn
Public Health Resources
B cell dysregulation in aging is thought to mostly occur in conventional B2 cells without affecting innate B1 cells. Elderly humans and mice also accumulate 4-1BBL+ MHC class-IHi CD86Hi B cells of unknown origin. In this article, we report that these cells, termed 4BL cells, are activated murine and possibly human B1a cells. The activation is mediated by aging human monocytes and murine peritoneal macrophages. They induce expression and activation of 4-1BBL and IFN-gR1 on B1a cells to subsequently upregulate membrane TNF-α and CD86. As a result, activated B1a/4BL cells induce expression of granzyme B in CD8+ T cells by …