Titre du document / Document title

Functions of metallothionein generating interleukin-10-producing regulatory CD4⁺ T cells potentiate suppression of collagen-induced arthritis

Auteur(s) / Author(s)

HUH Sungjin ⁽¹⁾ ; LEE Kyuheon ⁽²⁾ ; YUN Hye-Sun ⁽¹⁾ ; PAIK Doo-Jin ⁽¹⁾ ; JUNG MOGG KIM ⁽³⁾ ; YOUN Jeehee ^{(1 2)} ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Department of Anatomy and Cell Biology, College of Medicine, Hanyang University, Seoul, COREE, REPUBLIQUE DE
⁽²⁾ Department of Biomedical Sciences and Institute of Biomedical Sciences, College of Medicine, Hanyang University, Seoul, COREE, REPUBLIQUE DE
⁽³⁾ Department of Microbiology, College of Medicine, Hanyang University, Seoul, COREE, REPUBLIQUE DE

Résumé / Abstract

Metallothionein, a cysteine-rich stress response protein that is naturally induced by a variety of immunologic stressors, has been shown to suppress autoimmune disorders through mechanisms not yet fully defined. In the present study, we examined the underlying mechanisms by which metallothionein might mediate such regulation of autoimmunity. Naive CD4⁺ T cells from metallothionein-deficient mice differentiated to produce significantly less IL-10, TGF-y, and repressor of GATA, but more IFN-γ and T-bet, when compared with those from wild-type mice. The levels of IL-4 and GATA-3 production were not different between the two groups of mice. Conversely, treatment with exogenous metallothionein during the priming phase drove naïve wild-type CD4 T cells to differentiate into cells producing more IL-10 and TGF-β, but less IFN-γ than untreated cells. Metallothionein-primed cells were hyporesponsive to restimulation, and suppressive to T cell proliferation in an IL-10-dependent manner. Lymphocytes from metallothionein-deficient mice displayed significantly elevated levels of AP-1 and JNK activities in response to stimulation compared with those from wild-type controls. Importantly, transgenic mice overexpressing metallothionein exhibited significantly reduced susceptibility to collagen-induced arthritis and enhanced IL-10 level in the serum, relative to their nontransgenic littermates. Taken together, these data suggest that metallothionein is able to promote the generation of IL-10- and TGF-β-producing type 1 regulatory T-like cells by downregulating JNK-dependent AP-1 activity. Thus, metallothionein may play an important role in the regulation of Thl-dependent autoimmune arthritis, and may represent both a potential target for therapeutic manipulation and a critical element in the diagnostic assessment of disease potential.

Revue / Journal Title

Journal of microbiology and biotechnology   ISSN 1017-7825 

Source / Source

2007, vol. 17, n^o2, pp. 348-358 [11 page(s) (article)] (55 ref.)

Langue / Language

Anglais

Editeur / Publisher

Korean Society for Applied Microbiology, Seoul, COREE, REPUBLIQUE DE  (1991) (Revue)

Mots-clés anglais / English Keywords

Cytokine ; Autoimmunity ; Collagen ; Suppression ; Regulation(control) ; Interleukin ; Metallothionein ;

Mots-clés français / French Keywords

Cytokine ; Autoimmunité ; Collagène ; Suppression ; Régulation ; Interleukine ; Métallothionéine ;

Mots-clés espagnols / Spanish Keywords

Citoquina ; Autoinmunidad ; Colágeno ; Supresión ; Regulación ; Interleuquina ; Metalotioneina ;

Mots-clés d'auteur / Author Keywords

Metallothionein ; interleukin-10 ; regulatory T cells ; arthritis ; autoimmunity ;

Localisation / Location

INIST-CNRS, Cote INIST : 26482, 35400014699905.0210