دورية أكاديمية
IL-6 selectively suppresses cDC1 specification via C/EBPβ.
| العنوان: | IL-6 selectively suppresses cDC1 specification via C/EBPβ. |
|---|---|
| المؤلفون: | Kim S; Department of Pathology and Immunology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA., Chen J; Department of Pathology and Immunology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA., Jo S; Department of Pathology and Immunology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA., Ou F; Department of Pathology and Immunology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA., Ferris ST; Department of Pathology and Immunology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA., Liu TT; Department of Pathology and Immunology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA., Ohara RA; Department of Pathology and Immunology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA., Anderson DA; Department of Pathology and Immunology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA., Wu R; Department of Pathology and Immunology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA., Chen MY; Department of Surgery, Washington University and Siteman Cancer Center in St. Louis, St. Louis, MO, USA., Gillanders WE; Department of Pathology and Immunology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA., Gillanders WE; Department of Surgery, Washington University and Siteman Cancer Center in St. Louis, St. Louis, MO, USA.; The Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University in St. Louis School of Medicine , St. Louis, MO, USA., Murphy TL; Department of Pathology and Immunology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA., Murphy KM; Department of Pathology and Immunology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA. |
| المصدر: | The Journal of experimental medicine [J Exp Med] 2023 Oct 02; Vol. 220 (10). Date of Electronic Publication: 2023 Jul 11. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Rockefeller University Press Country of Publication: United States NLM ID: 2985109R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1540-9538 (Electronic) Linking ISSN: 00221007 NLM ISO Abbreviation: J Exp Med Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: New York, NY : Rockefeller University Press |
| مواضيع طبية MeSH: | Interleukin-6* , Cytokines*, Humans ; Animals ; Mice ; Binding Sites ; Dendritic Cells ; Homeostasis |
| مستخلص: | Cytokines produced in association with tumors can impair antitumor immune responses by reducing the abundance of type 1 conventional dendritic cells (cDC1), but the mechanism remains unclear. Here, we show that tumor-derived IL-6 generally reduces cDC development but selectively impairs cDC1 development in both murine and human systems through the induction of C/EBPβ in the common dendritic cell progenitor (CDP). C/EBPβ and NFIL3 compete for binding to sites in the Zeb2 -165 kb enhancer and support or repress Zeb2 expression, respectively. At homeostasis, pre-cDC1 specification occurs upon Nfil3 induction and consequent Zeb2 suppression. However, IL-6 strongly induces C/EBPβ expression in CDPs. Importantly, the ability of IL-6 to impair cDC development is dependent on the presence of C/EBPβ binding sites in the Zeb2 -165 kb enhancer, as this effect is lost in Δ1+2+3 mutant mice in which these binding sites are mutated. These results explain how tumor-associated IL-6 suppresses cDC1 development and suggest therapeutic approaches preventing abnormal C/EBPβ induction in CDPs may help reestablish cDC1 development to enhance antitumor immunity. (© 2023 Kim et al.) |
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| معلومات مُعتمدة: | R21 AI163421 United States AI NIAID NIH HHS; R01 CA248919 United States CA NCI NIH HHS; R01 AI162643 United States AI NIAID NIH HHS; T32 AR007279 United States AR NIAMS NIH HHS; P30 CA091842 United States CA NCI NIH HHS; R21 AI164142 United States AI NIAID NIH HHS; F30 HL167565 United States HL NHLBI NIH HHS; T32 CA009621 United States CA NCI NIH HHS; R01 AI150297 United States AI NIAID NIH HHS |
| المشرفين على المادة: | 0 (Interleukin-6) 0 (Cytokines) |
| تواريخ الأحداث: | Date Created: 20230711 Date Completed: 20230713 Latest Revision: 20240425 |
| رمز التحديث: | 20240425 |
| مُعرف محوري في PubMed: | PMC10336151 |
| DOI: | 10.1084/jem.20221757 |
| PMID: | 37432392 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1540-9538 |
|---|---|
| DOI: | 10.1084/jem.20221757 |