The alarmin IL-33 activates type 1 and type 2 immune cells via its receptor ST2 in a context-specific manner. We discovered a type 1 immunity-restricted promoter of the ST2-coding gene Il1rl1, which is located far upstream of the curated gene and is crucial for antiviral CD8+ cytotoxic T cell and CD4+ TH1 cell responses.
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References
Schmitz, J. et al. IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines. Immunity 23, 479–490 (2005). This paper reports on the identification of IL-33 as the ligand for ST2 and highlights its importance in type 2 immunity.
Bonilla, W. V. et al. The alarmin interleukin-33 drives protective antiviral CD8+ T cell responses. Science 335, 984–989 (2012). This paper reports on the vital role of IL-33–ST2 signaling for protective antiviral CD8+ T cell responses.
Baumann, C. et al. T-bet- and STAT4-dependent IL-33 receptor expression directly promotes antiviral Th1 cell responses. Proc. Natl Acad. Sci. USA 112, 4056–4061 (2015). This paper reports on the transcriptional and quantitative regulation of ST2 expression and its function in antiviral CD4+ TH1 cell responses.
Peine, M., Marek, R. M. & Löhning, M. IL-33 in T cell differentiation, function, and immune homeostasis. Trends Immunol. 37, 321–333 (2016). A review article that highlights the qualitative and quantitative differences in ST2 expression between T cell subsets and the control by lineage-specifying transcription factors.
Dwyer, G. K., D’Cruz, L. M. & Turnquist, H. R. Emerging functions of IL-33 in homeostasis and immunity. Annu. Rev. Immunol. 40, 15–43 (2022). A review article that discusses the role of IL-33 in tissue homeostasis and disease.
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This is a summary of: Brunner, T. M. et al. A type 1 immunity-restricted promoter of the IL-33 receptor gene directs antiviral T-cell responses. Nat. Immunol. https://doi.org/10.1038/s41590-023-01697-6 (2024).
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Type 1 or type 2 lineage-specific promoters regulate expression of the IL-33 receptor in T cells. Nat Immunol 25, 204–205 (2024). https://doi.org/10.1038/s41590-023-01706-8
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DOI: https://doi.org/10.1038/s41590-023-01706-8
