IL-21 Is Produced by Th17 Cells and Drives IL-17 Production in a STAT3-dependent Manner*

By Lai Wei, A. Laurence, K. Elias, J. O’Shea. Journal of Biological Chemistry, 2007

693 citations recorded by the source corpus.

CD4+ helper T cells can differentiate into several possible fates including: Th1, Th2, T regulatory, and Th17 cells. Although, cytokine production by non-T cells is an important factor in helper T cell differentiation, a characteristic feature of both Th1 and Th2 lineages is their ability to secrete cytokines that promote their respective differentiation. However, cytokines produced by T cells that help to sustain Th17 cells have not yet been identified. Here we show that IL-21 is a product of Th17 cells, which is induced in a Stat3-dependent manner. Additionally, Stat3 can directly bind the Il21 promoter. IL-21 also induces IL-17 production and expression of the transcription factor, RORγt. Furthermore, generation of Th17 cells in the conventional manner is attenuated by blocking IL-21. IL-21 is known to activate Stat3 and its ability to induce Th17 differentiation is abrogated in the absence of Stat3. These data argue that IL-21 serves as an autocrine factor secreted by Th17 cells that promotes or sustains Th17 lineage commitment.

Subfields: Immunology, Pathology and Forensic Medicine

View Paper: https://www.semanticscholar.org/paper/83ae05d3a9be0a1877cb520c3920c7171e0e92ea

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

1. W. E. Paul
2. Jinfang Zhu
3. Dan R. Littman
4. V. Kuchroo
5. C. Dong
6. J. O’Shea
7. T. Korn
8. M. Oukka

In Pathology and Forensic Medicine

1. T. Korn
2. F. Powrie
3. W. E. Paul
4. C. Dong
5. Dan R. Littman
6. Jinfang Zhu
7. E. Bettelli
8. M. Oukka

Citations in the corpus

• Cytokine signaling modules in inflammatory responses. (2008, background): “However, Stat3 also directly regulates the expression of Il21 and Il17 (Chen et al., 2006; Wei et al., 2007).”
• Global mapping of H3K4me3 and H3K27me3 reveals specificity and plasticity in lineage fate determination of differentiating CD4+ T cells. (2009, background): “IL-6, IL-21, and IL-23 all signal through Stat3, and in combination with TGFb-1 induce the transcription factors RORgt and RORa (Chen et al., 2006; Dong, 2008; Korn et al., 2007; Nurieva et al., 2007; Wei et al., 2007; Yang et al., 2008a; Zhou et al., 2007).”
• Diverse Targets of the Transcription Factor STAT3 Contribute to T Cell Pathogenicity and Homeostasis (2010, methodology): “Mice Cd4 Cre; Stat3 mice were generated as previously described (Lee et al., 2002; Wei et al., 2007).”
• IL-17 and Th17 Cells. (2009, background): “However, STAT3 also binds directly to the Il17 and Il21 promoters (25, 58).”
• TH17 cells in development: an updated view of their molecular identity and genetic programming (2008, background): “Products of T H 17 cells and their function Although the hallmark of T H 17 cells is the expression of IL-17, additional molecules have been identified by microarray analysis as being selectively expressed by T H 17 cell”
• A critical function for transforming growth factor-β, interleukin 23 and proinflammatory cytokines in driving and modulating human TH-17 responses (2008, background): “Mouse T H -17 cells produce not only IL-17 but also IL-21 (ref”