Regulation of an Autoimmune Model for Multiple Sclerosis in Th2-Biased GATA3 Transgenic Mice

Abstract

T helper (Th)2 cells have been proposed to play a neuroprotective role in multiple sclerosis (MS). This is mainly based on “loss-of-function” studies in an animal model for MS, experimental autoimmune encephalomyelitis (EAE), using blocking antibodies against Th2 related cytokines, and knockout mice lacking Th2-related molecules. We tested whether an increase of Th2 responses (“gain-of-function” approach) could alter EAE, the approach of novel GATA binding protein 3 (GATA3)-transgenic (tg) mice that overexpress GATA3, a transcription factor required for Th2 differentiation. In EAE induced with myelin oligodendrocyte glycoprotein (MOG)35–55 peptide, GATA3-tg mice had a significantly delayed onset of disease and a less severe maximum clinical score, compared with wild-type C57BL/6 mice. Histologically, GATA3-tg mice had decreased levels of meningitis and demyelination in the spinal cord, and anti-inflammatory cytokine profiles immunologically, however both groups developed similar levels of MOG-specific lymphoproliferative responses. During the early stage, we detected higher levels of interleukin (IL)-4 and IL-10, with MOG and mitogen stimulation of regional lymph node cells in GATA3-tg mice. During the late stage, only mitogen stimulation induced higher IL-4 and lower interferon-γ and IL-17 production in GATA3-tg mice. These results suggest that a preexisting bias toward a Th2 immune response may reduce the severity of inflammatory demyelinating diseases, including MS.

Medium-dose estrogen ameliorates experimental autoimmune encephalomyelitis in ovariectomized mice

“…The suppressive function of T reg cells is directed by Foxp3; its high-level expression is associated with suppressive function in human and mouse CD4 þ T-cells (Liston & Gray 2014). As a master regulator of T H 2 cells, GATA3 is required for T H 2 cell differentiation, stability, and cytokine production (Chen et al 2014;Fernando et al 2014).…”

Angiotensin II Promotes the Development of Carotid Atherosclerosis in Type 2 Diabetes Patients via Regulating the T Cells Activities: A Cohort Study

“…Additionally, Th2 cells exert their effect by secreting a variety of immunological cytokines, including IL-4 which is mainly secreted by Th2 and induces Th2 differentiation [31]. GATA3 selectively induces initial CD4+ T cells into Th2 cells [32]. It is still controversial about the role of Th2-type immune response in the process of development of atherosclerosis.…”

Organ-specific protective role of NKT cells in virus-induced inflammatory demyelination and myocarditis depends on mouse strain

“…The culture supernatants were harvested and stored at −80°C until examined. The concentrations of IL-4, IL-10, and IFN-γ in the culture supernatants were quantified by ELISA (BD Biosciences, San Diego, CA), according to the manufacturer’s instructions (Fernando et al., 2014). …”