Excess IL-1 signaling enhances the development of Th17 cells by downregulating TGF-β-induced Foxp3 expression

IL-1R antagonist-deficient (Il1rn(-/-)) mice develop autoimmune arthritis in which IL-17A plays a crucial role. Although many studies have shown that Th17 cell differentiation is dependent on TGF-β and IL-6, we found that Th17 cells developed normally in Il1rn(-/-)Il6(-/-) mice in vivo. Then, we ana...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:The Journal of immunology (1950) 2014-02, Vol.192 (4), p.1449-1458
Hauptverfasser: Ikeda, Satoshi, Saijo, Shinobu, Murayama, Masanori A, Shimizu, Kenji, Akitsu, Aoi, Iwakura, Yoichiro
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:IL-1R antagonist-deficient (Il1rn(-/-)) mice develop autoimmune arthritis in which IL-17A plays a crucial role. Although many studies have shown that Th17 cell differentiation is dependent on TGF-β and IL-6, we found that Th17 cells developed normally in Il1rn(-/-)Il6(-/-) mice in vivo. Then, we analyzed the mechanisms of Th17 cell differentiation in Il1rn(-/-)Il6(-/-) mice. We found that IL-21 production was increased in the lymph nodes of Il1rn(-/-) mice, naive Il6(-/-) CD4(+) T cells differentiated into Th17 cells when cultured with TGF-β and IL-21, and the differentiation was greatly enhanced when IL-1 was added to the culture. Th17 cell differentiation was not induced by either TGF-β or IL-1 alone or in combination. IL-21 induced IL-1R expression in naive CD4(+) T cells, and IL-1 inhibited TGF-β-induced Foxp3 expression, resulting in the promotion of Th17 cell differentiation. Furthermore, IL-1 augmented the expression of Th17 cell-specific transcription factors such as Nfkbiz and Batf. These results indicate that excess IL-1 signaling can overcome the requirement of IL-6 in the differentiation of Th17 cells by suppressing Foxp3 expression and inducing Th17 cell-specific transcription factors.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.1300387