Browsing by Subject "STAT6 Transcription Factor"

Now showing 1 - 4 of 4
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    STAT6 and Furin Are Successive Triggers for the Production of TGF-β by T Cells
    (The American Association of Immunologists, Inc., 2018-11) Li, Yue; Liu, Weiren; Guan, Xiaqun; Truscott, Jamie; Creemers, John W.; Chen, Hung-Lin; Pesu, Marko; El Abiad, Rami G.; Karacay, Bahri; Urban, Joseph F.; Elliott, David E.; Kaplan, Mark H.; Blazar, Bruce R.; Ince, M. Nedim; Pediatrics, School of Medicine
    Production of TGF-β by T cells is key to various aspects of immune homeostasis, with defects in this process causing or aggravating immune-mediated disorders. The molecular mechanisms that lead to TGF-β generation by T cells remain largely unknown. To address this issue, we take advantage of the fact that intestinal helminths stimulate Th2 cells besides triggering TGF-β generation by T lymphocytes and regulate immune-mediated disorders. We show that the Th2 cell-inducing transcription factor STAT6 is necessary and sufficient for the expression of TGF-β propeptide in T cells. STAT6 is also necessary for several helminth-triggered events in mice, such as TGF-β-dependent suppression of alloreactive inflammation in graft-versus-host disease. Besides STAT6, helminth-induced secretion of active TGF-β requires cleavage of propeptide by the endopeptidase furin. Thus, for the immune regulatory pathway necessary for TGF-β production by T cells, our results support a two-step model, composed of STAT6 and furin.
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    STAT6-mediated keratitis and blepharitis: a novel murine model of ocular atopic dermatitis
    (Association for Research in Vision and Opthalmology, 2014-06) Turner, Matthew J.; DaSilva-Arnold, Sonia; Luo, Na; Hu, Xinyao; West, Callah C.; Sun, Lou; Hall, Christopher; Bradish, Joshua; Kaplan, Mark H.; Travers, Jeffrey B.; Sun, Yang; Department of Ophthalmology, IU School of Medicine
    PURPOSE: Atopic dermatitis (AD) is a common inflammatory disease that can affect the eye, resulting in ocular pathologies, including blepharitis, keratitis, and uveitis; however, the pathogenic mechanisms underlying the ocular manifestations of AD are not well understood. METHODS: In the present study, we characterized the ocular pathologies that develop in the Stat6VT mouse model of AD. We examined the cytokine profile of the eyelid lesions, measured the behavioral response, and documented the treatment response to topical steroids. RESULTS: Our results show that Stat6VT mice spontaneously developed blepharitis, keratitis, and uveitis similar to that observed in patients with AD. Histologic findings of allergic inflammation in affected eyelids in this model include the presence of a lymphocyte-predominant infiltrate and tissue eosinophilia in the dermis. Gene expression analysis of affected eyelid tissue by quantitative PCR revealed increased amounts of mRNAs for the Th2 cytokines IL-4, IL-5, and IL-13. In addition, increased eyelid scratching was seen in Stat6VT mice with blepharitis. Topical treatment with the corticosteroid clobetasol reduced eyelid inflammation, tissue eosinophilia, and Th2 cytokine expression. CONCLUSIONS: The development of AD-like ocular pathologies in this model supports the idea that in humans, AD-associated disease of the eye may be driven by Th2-mediated inflammation and demonstrates that the Stat6VT mouse may be a useful system in which to further investigate pathogenesis of and treatment strategies for blepharitis and other ocular diseases that develop in association with AD.
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    Toxic interaction between Th2 cytokines and Staphylococcus aureus in atopic dermatitis
    (Nature Publishing Group, 2014-08) Travers, Jeffrey B.; Department of Dermatology, IU School of Medicine
    Patients with atopic dermatitis (AD) are commonly colonized/infected with Staphylococcus aureus, and this bacterium is known to worsen the dermatitis. In this issue, Brauweiler et al. demonstrate a newly discovered mechanism by which Th2 cytokines involved in AD augments the toxicity of the lytic staphylococcal protein alpha toxin. This review presents mechanisms by which Th2 cytokines may interact with S. aureus to the detriment of the dermatitis.