• Cd4+ T cell-specific proteomic pathways identified in progression of hypertension across postmenopausal transition

      Uhlorn, J.A.; Husband, N.A.; Romero-Aleshire, M.J.; Moffett, C.; Lindsey, M.L.; Langlais, P.R.; Brooks, H.L.; Department of Physiology, College of Medicine, University of Arizona; Department of Medicine, College of Medicine, University of Arizona (American Heart Association Inc., 2021)
      BACKGROUND: Menopause is associated with an increase in the prevalence and severity of hypertension in women. Although premenopausal females are protected against T cell-dependent immune activation and development of angiotensin II (Ang II) hypertension, this protection is lost in postmenopausal females. Therefore, the current study hypothesized that specific CD4+ T cell pathways are regulated by sex hormones and Ang II to mediate progression from premenopausal protection to postmenopausal hypertension. METHODS AND RESULTS: Menopause was induced in C57BL/6 mice via repeated 4-vinylcyclohexene diepoxide injections, while premenopausal females received sesame oil vehicle. A subset of premenopausal mice and all menopausal mice were infused with Ang II for 14 days (Control, Ang II, Meno/Ang II). Proteomic and phosphoproteomic profiles of CD4+ T cells isolated from spleens were examined. Ang II markedly increased CD4+ T cell protein abundance and phosphorylation associated with DNA and histone methylation in both premenopausal and postmenopausal females. Compared with premenopausal T cells, Ang II infusion in menopausal mice increased T cell phosphorylation of MP2K2, an upstream regulator of ERK, and was associated with upregulated phosphorylation at ERK targeted sites. Additionally, Ang II infusion in menopausal mice decreased T cell phosphorylation of TLN1, a key regulator of IL-2Rα and FOXP3 expression. CONCLUSIONS: These findings identify novel, distinct T cell pathways that influence T cell-mediated inflammation during postmenopausal hypertension. © 2021 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.
    • Chronic immune barrier dysregulation among women with a history of violence victimization

      Swaims-Kohlmeier, Alison; Haddad, Lisa B; Li, Zheng-Rong Tiger; Brookmeyer, Kathryn A; Baker, James M; Widom, Cathy Spatz; Lamousin, James C; Chi, Kai-Hua; Chen, Cheng Y; Kersh, Ellen N; et al. (AMER SOC CLINICAL INVESTIGATION INC, 2019-05-16)
      We explored the association between violence victimization and increased risk for acquiring sexually transmitted infections (STIs) in women by measuring cellular immune barrier properties from the female reproductive tract. STI-negative participants reporting repeated prior victimization occurrences through the lifetime trauma and victimization history (LTVH) instrument were more likely to exhibit alterations in barrier homeostasis and the composition of critical immune mediators irrespective of demographic parameters or presence of bacterial vaginosis. By combining cellular data with mixed-effect linear modeling, we uncovered differences in local T cells, MHCII+ antigen-presenting cells, and epithelial cells indicative of altered trafficking behavior, increased immunosuppressive function, and decreased barrier integrity at sites of STI exposure that correlate most strongly with LTVH score. These data evidence a biological link between a history of violence victimization and risk of STI acquisition through immune dysregulation in the female reproductive tract.
    • Cytomegalovirus (CMV) research in immune senescence comes of age: overview of the 6th International Workshop on CMV and Immunosenescence

      Nikolich-Žugich, Janko; van Lier, René A W; Univ Arizona, Coll Med, Dept Immunobiol; Univ Arizona, Coll Med, Arizona Ctr Aging; Univ Arizona, Inst BIO5 (SPRINGER, 2017-06-01)
      Cytomegalovirus (CMV) is one of the most complex and most ubiquitous latent persistent viruses, with a considerable ability to evade and manipulate the immune system. Following an early-life infection, most immunocompetent humans spend several decades living with CMV, and, because the virus in these hosts does not cause manifest disease, CMV can be considered part of normal aging for more than half of humanity. However, there is accumulating evidence that CMV carriage is not a null event and that both potentially harmful and potentially beneficial outcomes emanate from the interaction of CMV with its mammalian hosts. This article provides an overview of the 6th International Workshop on CMV and Immunosenescence, highlighting the advances in the field made in the past two years, as related to CMV epidemiology/geroscience, CMV virology with an accent on latency, and CMV immune evasion and immune recognition of the virus and its antigens.