Regulation of an autoimmune model for multiple sclerosis in Th2-biased GATA3 transgenic mice.
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.
Department of Microbiology and Immunology, Center for Tumor and Molecular Virology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA. viromi.fernando@gmail.com.
Viromi
V
Fernando
Department of Microbiology and Immunology, Center for Tumor and Molecular Virology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA. omura.s@hotmail.com.
Seiichi
S
Omura
Department of Microbiology and Immunology, Center for Tumor and Molecular Virology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA. fsato@lsuhsc.edu.
Fumitaka
F
Sato
Department of Microbiology and Immunology, Center for Tumor and Molecular Virology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA. ekawai-thk@umin.ac.jp.
Eiichiro
E
Kawai
Department of Microbiology and Immunology, Center for Tumor and Molecular Virology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA. nmarti@lsuhsc.edu.
Nicholas E
NE
Martinez
Department of Microbiology and Immunology, Center for Tumor and Molecular Virology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA. Iloveham2011@yahoo.com.
Sadie Faith
SF
Elliott
Department of Nephrology, Division of Clinical Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan. k-yohnpr@umin.ac.jp.
Keigyou
K
Yoh
Department of Anatomy and Embryology, Faculty of Medicine, International Institute for Integrative Sleep Medicine (WPI-IIIS), Life Science Center, Tsukuba Research Alliance (TARA), Laboratory Animal Resource Center (LARC), University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8575, Japan. satoruta@md.tsukuba.ac.jp.
Satoru
S
Takahashi
Department of Microbiology and Immunology, Center for Tumor and Molecular Virology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA. itsuno@lsuhsc.edu.
Ikuo
I
Tsunoda
D000818:Animals; D017252:CD3 Complex / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003711:Demyelinating Diseases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005260:Female; D050990:GATA3 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009103:Multiple Sclerosis / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D009154:Mutation; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology; D013116:Spinal Cord / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism*
D017252:CD3 Complex; D016207:Cytokines; D050990:GATA3 Transcription Factor; D063308:Myelin-Oligodendrocyte Glycoprotein