IL-1 family members and STAT activators induce cytokine production by Th2, Th17, and Th1 cells

• Published in: Proceedings of the National Academy of Sciences - PNAS 2009-08, Vol.106 (32), p.13463-13468
• Main Authors: Guo, Liying, Wei, Gang, Zhu, Jinfang, Liao, Wei, Leonard, Warren J, Zhao, Keji, Paul, William
• Format: Article
• Language: English
• Subjects: Allergies; Animals; Biological Sciences; Cells, Cultured; Cultured cells; Cytokines; Cytokines - biosynthesis; Family members; GATA3 Transcription Factor - metabolism; Interleukin-1 - metabolism; Interleukin-13 - metabolism; Interleukin-17 - metabolism; Interleukin-2 - biosynthesis; Interleukin-33; Interleukin-4 - metabolism; Interleukins; Interleukins - metabolism; Messenger RNA; Mice; NF-kappa B - metabolism; NFATC Transcription Factors - metabolism; p38 Mitogen-Activated Protein Kinases - metabolism; Phosphorylation; Receptors; Receptors, Antigen, T-Cell - metabolism; Receptors, Interleukin-1 - metabolism; rev genes; STAT Transcription Factors - metabolism; STAT5 Transcription Factor - metabolism; T lymphocytes; Th1 Cells - metabolism; Th2 Cells - metabolism; Up regulation
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0906988106

Expression of T1ST2, the IL-33R, by Th2 cells requires GATA3. Resting Th2 cells express little GATA3, which is increased by IL-33 and a STAT5 activator, in turn increasing T1ST2 from its low-level expression on resting Th2 cells. Th2 cells that have upregulated T1ST2 produce IL-13, but not IL-4, in response to IL-33 plus a STAT5 activator in an antigen-independent, NF-κB-dependent, cyclosporin A (CsA)-resistant manner. Similarly, Th17 cells produce IL-17A in response to IL-1β and a STAT3 activator and Th1 cells produce IFNγ in response to IL-18 and a STAT4 inducer. Thus, each effector Th cell produces cytokines without antigenic stimulation in response to an IL-1 family member and a specific STAT activator, implying an innate mechanism through which memory CD4 T cells are recruited by an induced cytokine environment.