IL-9 induces differentiation of TH17 cells and enhances function of FoxP3+ natural regulatory T cells.

Abstract

The development of T helper (T(H))17 and regulatory T (T(reg)) cells is reciprocally regulated by cytokines. Transforming growth factor (TGF)-beta alone induces FoxP3(+) T(reg) cells, but together with IL-6 or IL-21 induces T(H)17 cells. Here we demonstrate that IL-9 is a key molecule that affects differentiation of T(H)17 cells and T(reg) function. IL-9 predominantly produced by T(H)17 cells, synergizes with TGF-beta1 to differentiate naïve CD4(+) T cells into T(H)17 cells, while IL-9 secretion by T(H)17 cells is regulated by IL-23. Interestingly, IL-9 enhances the suppressive functions of FoxP3(+) CD4(+) T(reg) cells in vitro, and absence of IL-9 signaling weakens the suppressive activity of nT(regs) in vivo, leading to an increase in effector cells and worsening of experimental autoimmune encephalomyelitis. The mechanism of IL-9 effects on T(H)17 and T(regs) is through activation of STAT3 and STAT5 signaling. Our findings highlight a role of IL-9 as a regulator of pathogenic versus protective mechanisms of immune responses.

• Authors: Wassim Elyaman, Elizabeth M Bradshaw, Catherine Uyttenhove, Valérie Dardalhon, Amit Awasthi, Jaime Imitola, Estelle Bettelli, Mohamed Oukka, Jacques van Snick, Jean-Christophe Renauld, Vijay K Kuchroo, Samia J Khoury
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 106 Issue 31 Pg. 12885-90 (Aug 04 2009) ISSN: 1091-6490 [Electronic] United States
• PMID: 19433802 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Forkhead Transcription Factors
• Foxp3 protein, mouse
• Interleukin-17
• Interleukin-23
• Interleukin-9
• STAT3 Transcription Factor
• STAT5 Transcription Factor
• Stat3 protein, mouse
• Transforming Growth Factor beta1

Topics

• Amino Acid Sequence
• Animals
• Cell Differentiation (drug effects)
• Female
• Forkhead Transcription Factors (physiology)
• Interleukin-17 (biosynthesis)
• Interleukin-23 (pharmacology)
• Interleukin-9 (biosynthesis, pharmacology)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Molecular Sequence Data
• STAT3 Transcription Factor (physiology)
• STAT5 Transcription Factor (physiology)
• T-Lymphocytes, Regulatory (drug effects, physiology)
• Transforming Growth Factor beta1 (pharmacology)