Zinc suppresses Th17 development via inhibition of STAT3 activation

• Published in: International immunology Vol. 22; no. 5; pp. 375 - 386
• Main Authors: Kitabayashi, Chika, Fukada, Toshiyuki, Kanamoto, Minoru, Ohashi, Wakana, Hojyo, Shintaro, Atsumi, Toru, Ueda, Naoko, Azuma, Ichiro, Hirota, Hiroshi, Murakami, Masaaki, Hirano, Toshio
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01-05-2010
• Subjects: Animals; Arthritis, Experimental - drug therapy; Arthritis, Experimental - immunology; Arthritis, Experimental - pathology; autoimmune disease; Cells, Cultured; Humans; Interleukin-17 - immunology; Mice; Mice, Inbred C57BL; STAT3; STAT3 Transcription Factor - antagonists & inhibitors; STAT3 Transcription Factor - metabolism; Structure-Activity Relationship; Th17; Th17 Cells - cytology; Th17 Cells - drug effects; Th17 Cells - immunology; Th17 Cells - metabolism; Zinc; Zinc - pharmacology
• ISSN: 0953-8178; 1460-2377
• DOI: 10.1093/intimm/dxq017

Zinc (Zn) is an essential trace metal required by many enzymes and transcription factors for their activity or the maintenance of their structure. Zn has a variety of effects in the immune responses and inflammation, although it has not been well known how Zn affects these reactions on the molecular basis. We here showed that Zn suppresses Th17-mediated autoimmune diseases at lest in part by inhibiting the development of Th17 cells via attenuating STAT3 activation. In mice injected with type II collagen to induce arthritis, Zn treatment inhibited Th17 cell development. IL-6-mediated activation of STAT3 and in vitro Th17 cell development were all suppressed by Zn. Importantly, Zn binding changed the α-helical secondary structure of STAT3, disrupting the association of STAT3 with JAK2 kinase and with a phospho-peptide that included a STAT3-binding motif from the IL-6 signal transducer gp130. Thus, we conclude that Zn suppresses STAT3 activation, which is a critical step for Th17 development.