Cellular Stress in the Context of an Inflammatory Environment Supports TGF-β-Independent T Helper-17 Differentiation
| Autor: | Marc Veldhoen, Olivier Fesneau, Cristina Ferreira, Silvia Innocentin, Verena Brucklacher-Waldert, Marisa Stebegg, Julien C. Marie |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
XBP1 Cellular differentiation T cell differentiation Inflammation chemical and pharmacologic phenomena Biology Article General Biochemistry Genetics and Molecular Biology interleukin-17 Mice 03 medical and health sciences T helper cells 0302 clinical medicine cell stress Transforming Growth Factor beta Cellular stress response medicine Animals Humans Th17 cells lcsh:QH301-705.5 Cell growth T cell activation autoimmunity Cell Differentiation hemic and immune systems Acquired immune system Cell biology Mice Inbred C57BL 030104 developmental biology lcsh:Biology (General) 030220 oncology & carcinogenesis metabolic stress Interleukin 17 medicine.symptom Signal Transduction Transforming growth factor |
| Zdroj: | Cell Reports Cell Reports, Vol 19, Iss 11, Pp 2357-2370 (2017) |
| ISSN: | 2211-1247 |
| DOI: | 10.1016/j.celrep.2017.05.052 |
| Popis: | Summary T helper-17 (Th17) cells are associated with inflammatory disorders and cancer. We report that environmental conditions resulting in cellular stress, such as low oxygen, glucose, and isotonic stress, particularly enhance the generation of Th17 cells. Pharmacological inhibition of cell stress reduces Th17 cell differentiation while stress inducers enhance the development of Th17 cells. The cellular stress response results in Th17 cell development via sustained cytoplasmic calcium levels and, in part, XBP1 activity. Furthermore, in an inflammatory environment, conditions resulting in cell stress can bring about de novo Th17 cell differentiation, even in the absence of transforming growth factor β (TGF-β) signaling. In vivo, cell stress inhibition enhances resistance to Th17-mediated autoimmunity while stress-exposed T cells enhance disease severity. Adverse metabolic environments during inflammation provide a link between adaptive immunity and inflammation and may represent a risk factor for the development of chronic inflammatory conditions by facilitating Th17 cell differentiation. Graphical Abstract Highlights • Limited metabolite availability results in cellular stress • Cellular stress enhances Th17 cell polarization • Cellular stress induces de novo Th17 cell differentiation • Cellular stress can substitute for TGF-β in Th17 cell differentiation Brucklacher-Waldert et al. show how environmental conditions resulting in cellular stress, such as low metabolite levels, specifically enhance Th17 cell differentiation. Under inflammatory conditions, this stress can substitute for TGF-β signaling resulting in de novo Th17 cell differentiation. |
| Databáze: | OpenAIRE |
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