Zinc suppresses Th17 development via inhibition of STAT3 activation.
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 T(h)17-mediated autoimmune diseases at lest in part by inhibiting the development of T(h)17 cells via attenuating STAT3 activation. In mice injected with type II collagen to induce arthritis, Zn treatment inhibited T(h)17 cell development. IL-6-mediated activation of STAT3 and in vitro T(h)17 cell development were all suppressed by Zn. Importantly, Zn binding changed the alpha-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 T(h)17 development.
Kitabayashi
Chika
C
Laboratory of Developmental Immunology, JST-CREST, Graduate School of Frontier Biosciences, Graduate School of Medicine and WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan.
Fukada
Toshiyuki
T
Kanamoto
Minoru
M
Ohashi
Wakana
W
Hojyo
Shintaro
S
Atsumi
Toru
T
Ueda
Naoko
N
Azuma
Ichiro
I
Hirota
Hiroshi
H
Murakami
Masaaki
M
Hirano
Toshio
T
D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D002478:Cells, Cultured; D006801:Humans; D020381:Interleukin-17 / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D058504:Th17 Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D015032:Zinc / Q000494:pharmacology*
D020381:Interleukin-17; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C494087:Stat3 protein, mouse; D015032:Zinc