Browsing by Subject "Autoimmune"

Now showing 1 - 5 of 5
  • Thumbnail Image
    Item
    CD4+ T cell expression of the IL-10 receptor is necessary for facial motoneuron survival after axotomy
    (BMC, 2020) Runge, Elizabeth M.; Iyer, Abhirami K.; Setter, Deborah O.; Kennedy, Felicia M.; Sanders, Virginia M.; Jones, Kathryn J.; Anatomy and Cell Biology, School of Medicine
    Background: After peripheral nerve transection, facial motoneuron (FMN) survival depends on an intact CD4+ T cell population and a central source of interleukin-10 (IL-10). However, it has not been determined previously whether CD4+ T cells participate in the central neuroprotective IL-10 cascade after facial nerve axotomy (FNA). Methods: Immunohistochemical labeling of CD4+ T cells, pontine vasculature, and central microglia was used to determine whether CD4+ T cells cross the blood-brain barrier and enter the facial motor nucleus (FMNuc) after FNA. The importance of IL-10 signaling in CD4+ T cells was assessed by performing adoptive transfer of IL-10 receptor beta (IL-10RB)-deficient CD4+ T cells into immunodeficient mice prior to injury. Histology and qPCR were utilized to determine the impact of IL-10RB-deficient T cells on FMN survival and central gene expression after FNA. Flow cytometry was used to determine whether IL-10 signaling in T cells was necessary for their differentiation into neuroprotective subsets. Results: CD4+ T cells were capable of crossing the blood-brain barrier and associating with reactive microglial nodules in the axotomized FMNuc. Full induction of central IL-10R gene expression after FNA was dependent on CD4+ T cells, regardless of their own IL-10R signaling capability. Surprisingly, CD4+ T cells lacking IL-10RB were incapable of mediating neuroprotection after axotomy and promoted increased central expression of genes associated with microglial activation, antigen presentation, T cell co-stimulation, and complement deposition. There was reduced differentiation of IL-10RB-deficient CD4+ T cells into regulatory CD4+ T cells in vitro. Conclusions: These findings support the interdependence of IL-10- and CD4+ T cell-mediated mechanisms of neuroprotection after axotomy. CD4+ T cells may potentiate central responsiveness to IL-10, while IL-10 signaling within CD4+ T cells is necessary for their ability to rescue axotomized motoneuron survival. We propose that loss of IL-10 signaling in CD4+ T cells promotes non-neuroprotective autoimmunity after FNA.
  • Thumbnail Image
    Item
    Lymphocytic myocarditis with suspected granulomatosis with polyangiitis presenting as cardiogenic shock, restrictive cardiomyopathy and complete heart block
    (Elsevier, 2021-02) Anderson, Wesley L.; Bahrami, Mubashir H.; Guglin, Maya; Rao, Roopa; Medicine, School of Medicine
    We report a case of restrictive cardiomyopathy from lymphocytic myocarditis in a patient with suspected granulomatosis with polyangiitis (GPA). The case was complicated by complete heart block and renal failure. The diagnosis was supported by upper airway involvement, elevated serum serine proteinase 3 antibodies, and endomyocardial biopsy with lymphocytic infiltration. The patient responded appropriately to aggressive immunosuppressive therapy.
  • Thumbnail Image
    Item
    Neuroinflammation in Autoimmune Disease and Primary Brain Tumors: The Quest for Striking the Right Balance
    (Frontiers Media, 2021-08-13) Mitchell, Dana; Shireman, Jack; Potchanant, Elizabeth A. Sierra; Lara-Velazquez, Montserrat; Dey, Mahua; Pediatrics, School of Medicine
    According to classical dogma, the central nervous system (CNS) is defined as an immune privileged space. The basis of this theory was rooted in an incomplete understanding of the CNS microenvironment, however, recent advances such as the identification of resident dendritic cells (DC) in the brain and the presence of CNS lymphatics have deepened our understanding of the neuro-immune axis and revolutionized the field of neuroimmunology. It is now understood that many pathological conditions induce an immune response in the CNS, and that in many ways, the CNS is an immunologically distinct organ. Hyperactivity of neuro-immune axis can lead to primary neuroinflammatory diseases such as multiple sclerosis and antibody-mediated encephalitis, whereas immunosuppressive mechanisms promote the development and survival of primary brain tumors. On the therapeutic front, attempts are being made to target CNS pathologies using various forms of immunotherapy. One of the most actively investigated areas of CNS immunotherapy is for the treatment of glioblastoma (GBM), the most common primary brain tumor in adults. In this review, we provide an up to date overview of the neuro-immune axis in steady state and discuss the mechanisms underlying neuroinflammation in autoimmune neuroinflammatory disease as well as in the development and progression of brain tumors. In addition, we detail the current understanding of the interactions that characterize the primary brain tumor microenvironment and the implications of the neuro-immune axis on the development of successful therapeutic strategies for the treatment of CNS malignancies.
  • Thumbnail Image
    Item
    Pre- and post-conception planning in autoimmune disorders
    (2020-03) Kumar, Nimisha; Aksu, Eric; Gensel, Annie; Burger, Taylor; Pease, Kensey
    Background: Autoimmune diseases are often multisystem, requiring many specialists. However, there are no clear recommendations for many of these disorders for planning pregnancy and preventing exacerbations. Intervention: Little time is devoted to patient counseling about contraception or care antepartum, intrapartum, and postpartum. Contraception and many first-line interventions can have varying effects in different diseases, which can be further complicated by multiple diagnoses. Many of these disorders also can have postpartum complications, making follow-up essential. Results:Systemic lupus erythematosus (SLE) is known to cause exacerbations during pregnancy and has serious adverse outcomes for both mother and baby. Active disease is associated with higher rates of preterm birth, pre-eclampsia, thromboses, fetal loss, and neonatal lupus. Patients are at increased risk of these complications with a history of lupus nephritis, cessation of hydroxychloroquine, and primigravidity. Multiple sclerosis (MS) has lower rates of relapse during pregnancy, but higher rates in the first postpartum year. This has been attributed to the rapid increase in progesterone during pregnancy improving symptoms, while the rapid decrease after pregnancy promotes relapses. Additionally, neonatal morbidity does not increase as a result of MS. For other autoimmune diseases such as Sjögren's Syndrome or Grave’s Disease, the clinical picture may be complicated by the physiology of pregnancy, but is unclear whether pregnancy exacerbates the autoimmune component of the disease. Conclusions: Pregnancy and contraception could improve or worsen symptoms in autoimmune diseases, even up to a year postpartum. There is a significant gap in practice guidelines regarding contraception and pregnancy despite many diseases’ onset during childbearing years. Pregnancy and contraception counseling should be part of initial conversations at diagnosis to prepare women.
  • Thumbnail Image
    Item
    A Unique Case of Systemic Lupus Erythematosus Myocarditis Complicated by Plasmapheresis-Responsive Cardiogenic Shock
    (Elsevier, 2020-12-09) Smith, Carson; Guglin, Maya; Dougherty, Rachel E.; Rao, Roopa A.; Medicine, School of Medicine
    A 25-year-old woman with systemic lupus erythematosus complicated by biventricular failure with a history of multiple admissions presented with cardiogenic shock unresponsive to steroids, intravenous immunoglobulin, cyclophosphamide, and required extra-corporeal membrane oxygenation. Left ventricular function eventually recovered after plasmapheresis.