- Titel
- Role of Th17 Cells in the Pathogenesis of Amyotrophic Lateral Sclerosis
- Zitierfähige Url:
- https://nbn-resolving.org/urn:nbn:de:bsz:14-qucosa2-1011250
- Erstveröffentlichung
- 2025
- Datum der Einreichung
- 28.05.2025
- Datum der Verteidigung
- 08.12.2025
- Abstract (DE)
- Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder characterized by the progressive loss of motor neurons, yet its underlying pathogenic mechanisms remain incompletely understood. Increasing evidence suggests that neurodegeneration in ALS is not solely neuron-intrinsic but is critically shaped by immune dysregulation. This doctoral thesis investigates the role of adaptive immune responses, particularly T helper 17 (Th17) cells, in the pathogenesis and progression of ALS. Using a comprehensive and systematic immunophenotyping approach, this work characterizes peripheral and central immune profiles in a well-defined cohort of ALS patients. Through flow cytometry and cytokine analyses of peripheral blood mononuclear cells and cerebrospinal fluid, the thesis demonstrates a pronounced shift toward a pro-inflammatory immune state in ALS, marked by elevated Th1 and Th17 cells and a concomitant reduction in anti-inflammatory Th2 and regulatory T cells. Importantly, these immune alterations correlate with clinical disease severity and progression, underscoring their potential relevance as biomarkers. Building on these patient-derived findings, the dissertation further explores the direct neurotoxic effects of Th17 cells and their signature cytokine interleukin-17 (IL-17) using human induced pluripotent stem cell–derived motor neuron models. Co-culture experiments reveal that Th17 cells and IL-17 signaling impair motor neuron survival, providing mechanistic insight into how peripheral immune activation may directly contribute to motor neuron degeneration in ALS. Together, this work establishes a functional link between systemic immune imbalance and neurodegeneration in ALS, highlighting Th17-mediated inflammation as a key pathogenic driver and a promising therapeutic target. By integrating clinical immunology with human stem cell–based disease modeling, the dissertation advances our understanding of ALS as a systemic neuroinflammatory disease and lays the groundwork for immune-modulatory strategies in future ALS treatment.
- Freie Schlagwörter (DE)
- Amyotrophe Lateralsklerose (ALS), insbesondere T-Helfer-17-Zellen (Th17)
- Freie Schlagwörter (EN)
- Amyotrophic lateral sclerosis (ALS), particularly T helper 17 (Th17) cells
- Klassifikation (DDC)
- 610
- Klassifikation (RVK)
- YG 6304
- GutachterIn
- PD Dr. Rene Günther
- Prof. Dr. Lars Tönges
- Den akademischen Grad verleihende / prüfende Institution
- Technische Universität Dresden, Dresden
- Version / Begutachtungsstatus
- publizierte Version / Verlagsversion
- URN Qucosa
- urn:nbn:de:bsz:14-qucosa2-1011250
- Veröffentlichungsdatum Qucosa
- 12.01.2026
- Dokumenttyp
- Dissertation
- Sprache des Dokumentes
- Englisch
- Lizenz / Rechtehinweis
CC BY-NC-ND 4.0- Inhaltsverzeichnis
1. Introduction 1.1 Amyotrophic Lateral Sclerosis 1.1.1 Epidemiology, phenotype, and clinical characteristics 1.1.2 Genetics 1.1.3 Histopathology 1.1.4 Pathophysiology 1.2 Role of immune system in ALS 1.2.1 Glial cells as critical contributors to ALS pathogenesis 1.2.2 Role of peripheral immune cells in ALS pathogenesis 1.2.3 Correlation of immune system activation to clinical characteristics in ALS 1.2.4 Proinflammatory immune response caused by repetitive damage to neurons 1.3 Th17 cells and ALS 1.3.1 Definition and Differentiation of Th17 Cells 1.3.2 Th17 Cells and Their Role in Immune Response 1.3.3 Th17 cells in ALS 1.4 Modeling ALS with human induced pluripotent stem cells (hiPSCs) 2. Aim 3. Original research 3.1 Peripheral proinflammatory Th1/Th17 immune cell shift is linked to disease severity in amyotrophic lateral sclerosis (2020) 3.2 Interleukin17 and Th17 Lymphocytes Directly Impair Motoneuron Survival of Wildtype and FUSALS Mutant Human iPSCs (2021) 4. DISCUSSION 5. Summary 6. Zusammenfassung Reference Acknowledgments