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.
Keywords: autoimmune demyelinating diseases; GATA3 transcription factor; autoimmunity; animal models; paraffin; histology; oligodendrocyte-myelin glycoprotein; Th1-Th2 assays; Luxol fast blue; Th17; incomplete Freund’s adjuvant
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Fernando, V.; Omura, S.; Sato, F.; Kawai, E.; Martinez, N.E.; Elliott, S.F.; Yoh, K.; Takahashi, S.; Tsunoda, I. Regulation of an Autoimmune Model for Multiple Sclerosis in Th2-Biased GATA3 Transgenic Mice. Int. J. Mol. Sci. 2014, 15, 1700-1718.
Fernando V, Omura S, Sato F, Kawai E, Martinez NE, Elliott SF, Yoh K, Takahashi S, Tsunoda I. Regulation of an Autoimmune Model for Multiple Sclerosis in Th2-Biased GATA3 Transgenic Mice. International Journal of Molecular Sciences. 2014; 15(2):1700-1718.
Fernando, Viromi; Omura, Seiichi; Sato, Fumitaka; Kawai, Eiichiro; Martinez, Nicholas E.; Elliott, Sadie F.; Yoh, Keigyou; Takahashi, Satoru; Tsunoda, Ikuo. 2014. "Regulation of an Autoimmune Model for Multiple Sclerosis in Th2-Biased GATA3 Transgenic Mice." Int. J. Mol. Sci. 15, no. 2: 1700-1718.