IL-1β-mediated signals preferentially drive conversion of regulatory T cells but not conventional T cells into IL-17-producing cells.
Regulatory T cells (Tregs) are committed to suppressive functions. Recently, it was proposed that Tregs could produce IL-17 under proinflammatory, polarizing conditions. We studied the role of Tregs on IL-17 production in the absence of exogenous cytokines and insults. Using in vitro and in vivo approaches, we determined that under neutral conditions, simultaneous activation of Tregs and naive CD4(+) conventional T cells in the presence of APCs resulted in conversion of Tregs into IL-17-producing cells, and endogenous IL-1β was mandatory in this process. Mechanistic analysis revealed that the IL-1R1 was highly expressed on Tregs and that IL-1β induced marked activation of p38 and JNK, which were involved in IL-17 production. These observations could have important implications on therapeutic strategies using Tregs.
Li
Lequn
L
Department of Hematology-Oncology and Cancer Biology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston MA 02215, USA.
Kim
Jin
J
Boussiotis
Vassiliki A
VA
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D002469:Cell Separation; D018920:Coculture Techniques; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000276:immunology; D053583:Interleukin-1beta / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D048670:MAP Kinase Kinase 4 / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000276:immunology
D020381:Interleukin-17; D053583:Interleukin-1beta; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4
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