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| Item Type: | Article |
|---|---|
| Title: | A type 1 immunity-restricted promoter of the IL-33 receptor gene directs antiviral T-cell responses |
| Creators: |
Brunner, T.M.  ORCID: https://orcid.org/0000-0002-5279-2391, Serve, S. ORCID: https://orcid.org/0000-0002-9839-7119, Marx, A.F., Fadejeva, J., Saikali, P. ORCID: https://orcid.org/0000-0002-4916-7376, Dzamukova, M. ORCID: https://orcid.org/0000-0002-2389-3222, Durán-Hernández, N. ORCID: https://orcid.org/0000-0003-4253-0387, Kommer, C., Heinrich, F. ORCID: https://orcid.org/0000-0001-6097-5422, Durek, P., Heinz, G.A. ORCID: https://orcid.org/0000-0002-9330-3689, Höfer, T. ORCID: https://orcid.org/0000-0003-3560-8780, Mashreghi, M.F. ORCID: https://orcid.org/0000-0002-8015-6907, Kühn, R. ORCID: https://orcid.org/0000-0003-1694-9803, Pinschewer, D.D. ORCID: https://orcid.org/0000-0002-1594-3189 and Löhning, M. ORCID: https://orcid.org/0000-0001-6382-7281
|
| Abstract: | 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 T 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. |
| Keywords: | Alarmins, Antiviral Agents, Interleukin-1 Receptor-Like 1 Protein, Interleukin-33, T-Lymphocyte Subsets / Metabolism, Animals, Mice |
| Source: | Nature Immunology |
| ISSN: | 1529-2908 |
| Publisher: | Nature Publishing Group |
| Volume: | 25 |
| Number: | 2 |
| Page Range: | 256-267 |
| Date: | February 2024 |
| Official Publication: | https://doi.org/10.1038/s41590-023-01697-6 |
| PubMed: | View item in PubMed |
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