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Hypothermia promotes interleukin-22 expression and fine-tunes its biological activity
- Disturbed homeostasis as a result of tissue stress can provoke leukocyte responses enabling recovery. Since mild hypothermia displays specific clinically relevant tissue-protective properties and interleukin (IL)-22 promotes healing at host/environment interfaces, effects of lowered ambient temperature on IL-22 were studied. We demonstrate that a 5-h exposure of endotoxemic mice to 4°C reduces body temperature by 5.0° and enhances splenic and colonic il22 gene expression. In contrast, tumor necrosis factor-α and IL-17A were not increased. In vivo data on IL-22 were corroborated using murine splenocytes and human peripheral blood mononuclear cells (PBMC) cultured upon 33°C and polyclonal T cell activation. Upregulation by mild hypothermia of largely T-cell-derived IL-22 in PBMC required monocytes and associated with enhanced nuclear T-cell nuclear factor of activated T cells (NFAT)-c2. Notably, NFAT antagonism by cyclosporin A or FK506 impaired IL-22 upregulation at normothermia and entirely prevented its enhanced expression upon hypothermic culture conditions. Data suggest that intact NFAT signaling is required for efficient IL-22 induction upon normothermic and hypothermic conditions. Hypothermia furthermore boosted early signal transducer and activator of transcription 3 activation by IL-22 and shaped downstream gene expression in epithelial-like cells. Altogether, data indicate that hypothermia supports and fine-tunes IL-22 production/action, which may contribute to regulatory properties of low ambient temperature.
Author: | Evgeny Chichelnitskiy, Britta Himmelseher, Malte BachmannGND, Josef PfeilschifterGND, Heiko MühlORCiDGND |
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URN: | urn:nbn:de:hebis:30:3-457024 |
DOI: | https://doi.org/10.3389/fimmu.2017.00742 |
ISSN: | 1664-3224 |
Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/28706520 |
Parent Title (English): | Frontiers in immunology |
Publisher: | Frontiers Media |
Place of publication: | Lausanne |
Contributor(s): | Sofie Struyf |
Document Type: | Article |
Language: | English |
Year of Completion: | 2017 |
Date of first Publication: | 2017/06/29 |
Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Release Date: | 2018/02/27 |
Tag: | endotoxemia; hypothermia; interleukin-22; peripheral blood mononuclear cells; signal transducer and activator of transcription 3 |
Volume: | 8 |
Issue: | Art. 742 |
Page Number: | 14 |
First Page: | 1 |
Last Page: | 14 |
Note: | Copyright © 2017 Chichelnitskiy, Himmelseher, Bachmann, Pfeilschifter and Mühl. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
HeBIS-PPN: | 432256520 |
Institutes: | Medizin / Medizin |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Sammlungen: | Universitätspublikationen |
Licence (German): | Creative Commons - Namensnennung 4.0 |