Tissue alarmins and adaptive cytokine induce dynamic and distinct transcriptional responses in tissue-resident intraepithelial cytotoxic T lymphocytes.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
AuthorsZorro, Maria Magdalena
Weersma, Rinse K
Jonkers, Iris H
MetadataShow full item record
AbstractThe respective effects of tissue alarmins interleukin (IL)-15 and interferon beta (IFNβ), and IL-21 produced by T cells on the reprogramming of cytotoxic T lymphocytes (CTLs) that cause tissue destruction in celiac disease is poorly understood. Transcriptomic and epigenetic profiling of primary intestinal CTLs showed massive and distinct temporal transcriptional changes in response to tissue alarmins, while the impact of IL-21 was limited. Only anti-viral pathways were induced in response to all the three stimuli, albeit with differences in dynamics and strength. Moreover, changes in gene expression were primarily independent of changes in H3K27ac, suggesting that other regulatory mechanisms drive the robust transcriptional response. Finally, we found that IL-15/IFNβ/IL-21 transcriptional signatures could be linked to transcriptional alterations in risk loci for complex immune diseases. Together these results provide new insights into molecular mechanisms that fuel the activation of CTLs under conditions that emulate the inflammatory environment in patients with autoimmune diseases.
CitationJ Autoimmun. 2020 Feb 4:102422. doi: 10.1016/j.jaut.2020.102422.
AffiliationCiiM, Zentrum für individualisierte Infektionsmedizin, Feodor-Lynen-Str.7, 30625 Hannover.
JournalJournal of Autoimmunity
The following license files are associated with this item:
- Creative Commons
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-ShareAlike 4.0 International
- Distinct and Synergistic Contributions of Epithelial Stress and Adaptive Immunity to Functions of Intraepithelial Killer Cells and Active Celiac Disease.
- Authors: Setty M, Discepolo V, Abadie V, Kamhawi S, Mayassi T, Kent A, Ciszewski C, Maglio M, Kistner E, Bhagat G, Semrad C, Kupfer SS, Green PH, Guandalini S, Troncone R, Murray JA, Turner JR, Jabri B
- Issue date: 2015 Sep
- Reprogramming of CTLs into natural killer-like cells in celiac disease.
- Authors: Meresse B, Curran SA, Ciszewski C, Orbelyan G, Setty M, Bhagat G, Lee L, Tretiakova M, Semrad C, Kistner E, Winchester RJ, Braud V, Lanier LL, Geraghty DE, Green PH, Guandalini S, Jabri B
- Issue date: 2006 May 15
- Intestinal T-cell responses in celiac disease - impact of celiac disease associated bacteria.
- Authors: Sjöberg V, Sandström O, Hedberg M, Hammarström S, Hernell O, Hammarström ML
- Issue date: 2013
- Paradoxical coexpression of proinflammatory and down-regulatory cytokines in intestinal T cells in childhood celiac disease.
- Authors: Forsberg G, Hernell O, Melgar S, Israelsson A, Hammarström S, Hammarström ML
- Issue date: 2002 Sep
- Effect of redox status of peripheral blood on immune signature of circulating regulatory and cytotoxic T cells in streptozotocin induced rodent model of type I diabetes.
- Authors: Anupam K, Kaushal J, Prabhakar N, Bhatnagar A
- Issue date: 2018 Oct