| Autor: |
Max Löhning, Tobias Brunner, Sebastian Serve, Anna-Friederike Marx, Maria Dzamukova, Nayar Duran, Philippe Saikali, Christoph Kommer, Frederik Heinrich, Pawel Durek, Gitta Heinz, Thomas Höfer, Mir-Farzin Mashreghi, Ralf Kuehn, Daniel Pinschewer |
| Rok vydání: |
2023 |
| Popis: |
The pleiotropic alarmin interleukin-33 (IL-33) drives type-1, type-2, and regulatory T-cell responses via its receptor ST2. Subset-specific differences in ST2 expression intensity and dynamics suggest that transcriptional regulation is key in orchestrating the context-dependent activity of IL-33-ST2 signaling in T-cell immunity. Here, we identify a previously unrecognized alternative promoter in mice and humans that is located far upstream of the curated ST2-coding gene and drives ST2 expression in type-1 immunity. Mice lacking this promoter exhibit a selective loss of ST2 expression in type-1- but not type-2-biased immune cells, resulting in impaired expansion of cytotoxic T cells (CTLs) and T-helper-1 cells upon viral infection. T-cell-intrinsic IL-33 signaling via type-1 promoter-driven ST2 is critical to generate a clonally diverse population of antiviral short-lived effector CTLs. Thus, lineage-specific alternative promoter usage directs alarmin responsiveness in T-cell subsets and offers opportunities for immune cell-specific targeting of the IL-33-ST2 axis in infections and inflammatory diseases. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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