دورية أكاديمية

Unraveling IFN-I response dynamics and TNF crosstalk in the pathophysiology of systemic lupus erythematosus.

التفاصيل البيبلوغرافية
العنوان: Unraveling IFN-I response dynamics and TNF crosstalk in the pathophysiology of systemic lupus erythematosus.
المؤلفون: Van Eyndhoven LC; Laboratory of Immunoengineering, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, Netherlands.; Institute for Complex Molecular Systems (ICMS), Eindhoven University of Technology, Eindhoven, Netherlands., Chouri E; Laboratory of Immunoengineering, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, Netherlands.; Institute for Complex Molecular Systems (ICMS), Eindhoven University of Technology, Eindhoven, Netherlands., Matos CI; Laboratory of Immunoengineering, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, Netherlands.; Institute for Complex Molecular Systems (ICMS), Eindhoven University of Technology, Eindhoven, Netherlands., Pandit A; Center for Translational Immunology, Department of Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.; Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands., Radstake TRDJ; Center for Translational Immunology, Department of Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.; Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands., Broen JCA; Regional Rheumatology Center, Máxima Medical Center, Eindhoven and Veldhoven, Eindhoven, Netherlands., Singh A; Department of Electrical and Computer Engineering, University of Delaware, Newark, DE, United States., Tel J; Laboratory of Immunoengineering, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, Netherlands.; Institute for Complex Molecular Systems (ICMS), Eindhoven University of Technology, Eindhoven, Netherlands.
المصدر: Frontiers in immunology [Front Immunol] 2024 Mar 26; Vol. 15, pp. 1322814. Date of Electronic Publication: 2024 Mar 26 (Print Publication: 2024).
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101560960 Publication Model: eCollection Cited Medium: Internet ISSN: 1664-3224 (Electronic) Linking ISSN: 16643224 NLM ISO Abbreviation: Front Immunol Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [Lausanne : Frontiers Research Foundation]
مواضيع طبية MeSH: Interferon Type I* , Lupus Erythematosus, Systemic* , Autoimmune Diseases*, Humans ; Tumor Necrosis Factor-alpha ; Signal Transduction
مستخلص: Introduction: The innate immune system serves the crucial first line of defense against a wide variety of potential threats, during which the production of pro-inflammatory cytokines IFN-I and TNFα are key. This astonishing power to fight invaders, however, comes at the cost of risking IFN-I-related pathologies, such as observed during autoimmune diseases, during which IFN-I and TNFα response dynamics are dysregulated. Therefore, these response dynamics must be tightly regulated, and precisely matched with the potential threat. This regulation is currently far from understood.
Methods: Using droplet-based microfluidics and ODE modeling, we studied the fundamentals of single-cell decision-making upon TLR signaling in human primary immune cells (n = 23). Next, using biologicals used for treating autoimmune diseases [i.e., anti-TNFα, and JAK inhibitors], we unraveled the crosstalk between IFN-I and TNFα signaling dynamics. Finally, we studied primary immune cells isolated from SLE patients (n = 8) to provide insights into SLE pathophysiology.
Results: single-cell IFN-I and TNFα response dynamics display remarkable differences, yet both being highly heterogeneous. Blocking TNFα signaling increases the percentage of IFN-I-producing cells, while blocking IFN-I signaling decreases the percentage of TNFα-producing cells. Single-cell decision-making in SLE patients is dysregulated, pointing towards a dysregulated crosstalk between IFN-I and TNFα response dynamics.
Discussion: We provide a solid droplet-based microfluidic platform to study inherent immune secretory behaviors, substantiated by ODE modeling, which can challenge the conceptualization within and between different immune signaling systems. These insights will build towards an improved fundamental understanding on single-cell decision-making in health and disease.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.
(Copyright © 2024 Van Eyndhoven, Chouri, Matos, Pandit, Radstake, Broen, Singh and Tel.)
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معلومات مُعتمدة: 802791 International ERC_ European Research Council
فهرسة مساهمة: Keywords: ODE modeling; droplet-based microfluidics; heterogeneity; plasmacytoid dendritic cells; single-cell analysis; systemic lupus erythematosus; type I interferon
المشرفين على المادة: 0 (Tumor Necrosis Factor-alpha)
0 (Interferon Type I)
تواريخ الأحداث: Date Created: 20240410 Date Completed: 20240411 Latest Revision: 20240411
رمز التحديث: 20240411
مُعرف محوري في PubMed: PMC11002168
DOI: 10.3389/fimmu.2024.1322814
PMID: 38596672
قاعدة البيانات: MEDLINE
الوصف
تدمد:1664-3224
DOI:10.3389/fimmu.2024.1322814