Impaired expansion of regulatory T cells in a neonatal thymectomy-induced autoimmune mouse model.
Neonatal thymectomy in certain mouse strains is known to induce organ-specific autoimmunity due to impaired functions of T cells, including Foxp3(+) regulatory T (Treg) cells in the thymus. The precise mechanism underlying the induction of autoimmunity by neonatal thymectomy remains unclear. One possibility is that depletion of Treg cells breaks down peripheral tolerance. We examined the functions of Treg cells by using a murine Sjögren syndrome model of NFS/sld mice that underwent neonatal thymectomy. The ratio of Treg cells to effector memory phenotype T cells in thymectomy mice was significantly lower than that of nonthymectomy mice. In addition, in vitro induction of peripherally induced Treg cells by transforming growth factor-β (TGF-β) using naive T cells from Sjögren syndrome model mice was severely impaired. The mRNA expression of TGF-β receptor I and II and Smad3 and -4 in the TGF-β-induced signal transduction pathway of Treg cells in this Sjögren syndrome model were lower than those of control mice. In addition, Treg cells in this Sjögren syndrome model exhibited an interferon-γ-producing Th1-like phenotype that resembled effector T cells. In conclusion, these results suggest that abnormal expansion and differentiation of Treg cells and inflammatory cytokines produced by Treg cells contribute to the development of autoimmunity.
Department of Oral Molecular Pathology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
Akiko
A
Yamada
Department of Oral Molecular Pathology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
Aya
A
Ushio
Department of Oral Molecular Pathology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
Rieko
R
Arakaki
Department of Oral Molecular Pathology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
Takaaki
T
Tsunematsu
Department of Oral Molecular Pathology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
Yasusei
Y
Kudo
Department of Oral Molecular Pathology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
Yoshio
Y
Hayashi
Department of Oral Molecular Pathology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan. Electronic address: ishimaru.n@tokushima-u.ac.jp.
Naozumi
N
Ishimaru
D000818:Animals; D000831:Animals, Newborn; D015551:Autoimmunity; D002454:Cell Differentiation; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D007371:Interferon-gamma / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000276:immunology*; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000276:immunology*; D013047:Specific Pathogen-Free Organisms; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D013934:Thymectomy / Q000009:adverse effects; D016212:Transforming Growth Factor beta / Q000276:immunology* / Q000378:metabolism
D016207:Cytokines; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D007371:Interferon-gamma; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I