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

• Published in: The Journal of biological chemistry 2007-11, Vol.282 (48), p.34605-34610
• Main Authors: Wei, Lai, Laurence, Arian, Elias, Kevin M., O'Shea, John J.
• Format: Article
• Language: English
• Subjects: Animals; CD4-Positive T-Lymphocytes - metabolism; Cell Differentiation; Cell Lineage; Cytokines - metabolism; Gene Expression Regulation; Interleukin-17 - biosynthesis; Interleukins - biosynthesis; Mice; Mice, Inbred C57BL; Nuclear Receptor Subfamily 1, Group F, Member 3; Oligonucleotide Array Sequence Analysis; Promoter Regions, Genetic; Receptors, Retinoic Acid - metabolism; Receptors, Thyroid Hormone - metabolism; Spleen - cytology; STAT3 Transcription Factor - biosynthesis; STAT3 Transcription Factor - genetics; T-Lymphocytes - metabolism
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M705100200

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.