دورية أكاديمية
أعرض في EDS

Conversion of dendritic cells into tolerogenic or inflammatory cells depends on the activation threshold and kinetics of the mTOR signaling pathway.

التفاصيل البيبلوغرافية
العنوان: Conversion of dendritic cells into tolerogenic or inflammatory cells depends on the activation threshold and kinetics of the mTOR signaling pathway.
المؤلفون: Wixler V; Institute of Molecular Virology, Centre for Molecular Biology of Inflammation (ZMBE), Westfaelische Wilhelms- University, Von-Esmarch-Str. 56, 48149, Muenster, Germany. vwixler@uni-muenster.de., Boergeling Y; Institute of Molecular Virology, Centre for Molecular Biology of Inflammation (ZMBE), Westfaelische Wilhelms- University, Von-Esmarch-Str. 56, 48149, Muenster, Germany., Leite Dantas R; Institute of Molecular Virology, Centre for Molecular Biology of Inflammation (ZMBE), Westfaelische Wilhelms- University, Von-Esmarch-Str. 56, 48149, Muenster, Germany.; Department of Mental Health, Westfaelische Wilhelms-University, 48149, Muenster, Germany., Varga G; Pediatric Rheumatology and Immunology, University Children's Hospital Muenster, 48149, Muenster, Germany., Ludwig S; Institute of Molecular Virology, Centre for Molecular Biology of Inflammation (ZMBE), Westfaelische Wilhelms- University, Von-Esmarch-Str. 56, 48149, Muenster, Germany.
المصدر: Cell communication and signaling : CCS [Cell Commun Signal] 2024 May 21; Vol. 22 (1), pp. 281. Date of Electronic Publication: 2024 May 21.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: BioMed Central Country of Publication: England NLM ID: 101170464 Publication Model: Electronic Cited Medium: Internet ISSN: 1478-811X (Electronic) Linking ISSN: 1478811X NLM ISO Abbreviation: Cell Commun Signal Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : BioMed Central, c2003-
مواضيع طبية MeSH: Dendritic Cells*/immunology , Dendritic Cells*/metabolism , Dendritic Cells*/drug effects , TOR Serine-Threonine Kinases*/metabolism , Signal Transduction*/drug effects , Immune Tolerance*, Animals ; Mice ; Inflammation/metabolism ; Kinetics ; Lipopolysaccharides/pharmacology
مستخلص: Background: Restoring impaired peripheral immune tolerance is the primary challenge in treating autoimmune diseases. Our previous research demonstrated the effectiveness of small spleen peptides (SSPs), a fraction of low molecular weight proteins, in inhibiting the progression of psoriatic arthritis, even in the presence of high levels of the proinflammatory cytokine TNFα in the bloodstream. When specifically targeting dendritic cells (DCs), SSPs transform them into tolerogenic cells, which efficiently induce the development of regulatory Foxp3 + Treg cells. In this study, we provide further insights into the mechanism of action of SSPs.
Results: We found that SSPs stimulate the activation of the mTOR signaling pathway in dendritic cells, albeit in a different manner than the classical immunogenic stimulus LPS. While LPS-induced activation is rapid, strong, and sustained, the activity induced by SSPs is delayed, less intense, yet still significant. These distinct patterns of activation, as measured by phosphorylation of key components of the pathway are also observed in response to other immunogenic and tolerogenic stimuli such as GM-CSF + IL-4 or IL-10 and TGFβ. The disparity in mTOR activation between immunogenic and tolerogenic stimuli is quantitative rather than qualitative. In both cases, mTOR activation primarily occurs through the PI3K/Akt signaling axis and involves ERK and GSK3β kinases, with minimal involvement of AMPK or NF-kB pathways. Furthermore, in the case of SSPs, mTOR activation seems to involve adenosine receptors. Additionally, we observed that DCs treated with SSPs exhibit an energy metabolism with high plasticity, which is typical of tolerogenic cells rather than immunogenic cells.
Conclusion: Hence, the decision whether dendritic cells enter an inflammatory or tolerogenic state seems to rely on varying activation thresholds and kinetics of the mTOR signaling pathway.
(© 2024. The Author(s).)
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فهرسة مساهمة: Keywords: Dendritic cells; Immunogenesis; Peripheral immune tolerance; Small spleen peptides; Tolerogenesis; mTOR signaling cascade
تواريخ الأحداث: Date Created: 20240522 Date Completed: 20240522 Latest Revision: 20240529
رمز التحديث: 20240529
مُعرف محوري في PubMed: PMC11106905
DOI: 10.1186/s12964-024-01655-1
PMID: 38773618
قاعدة البيانات: MEDLINE
الوصف
تدمد:1478-811X
DOI:10.1186/s12964-024-01655-1