- Author
-
J. Chen
- Title
- Deconvolution of the interleukin-17 pathway in the pathobiology of spondyloarthritis
- Supervisors
- Co-supervisors
- Award date
- 8 June 2020
- Number of pages
- 227
- Document type
- PhD thesis
- Faculty
- Faculty of Medicine (AMC-UvA)
- Abstract
-
Spondyloarthritis (SpA) is the second most prevalent form of chronic inflammatory arthritis. There is an unmet clinical need for the treatment of inflammation and bone pathology in SpA patients. Inflammation affects the axial and peripheral joints and may additionally occur in the skin, eye, and gut. SpA is also characterized by pathologic bone formation in peripheral and axial skeletal sites. The ultimate therapeutic goal for SpA would be to develop interventions that suppress both inflammation and pathologic bone formation, and to bring patients into remission. Recent evidence indicates that Interleukin (IL)-17A is a key proinflammatory cytokine in SpA. This thesis presents novel insights on the biology of the IL-17-pathway in SpA, and suggestions for improving the therapeutic efficacy of targeting this pathway.
The novel findings include the tissue-specificity of IL-17A and IL-17F expression in skin and joint inflammation, and the observation that IL-17A+ mast cells can serve as cellular reservoirs of IL-17A. We present preclinical rationales for two novel small molecule treatments that are aimed at targeting cellular sources of IL-17A and modifying pathologic bone formation. Additionally, we identified the function of a previously unexplored IL-17 family cytokine in the disease-context of SpA. This thesis provides the basis for the continued exploration of the tissue-specific differences in the expression and function of IL-17 family members that may underlie the tissue-dependent responses to therapy. Altogether, these novel insights into IL-17 biology in SpA have potential implications for future therapeutic development in SpA. - Persistent Identifier
- https://hdl.handle.net/11245.1/04e58a5d-2e3e-4090-8a6a-daadaadff2e6
- Downloads
-
Thesis (complete)
Front matter
Contents
Chapter 1: General introduction
Chapter 2: Histologic evidence that mast cells contribute to local tissue inflammation in peripheral spondyloarthritis by regulating interleukin-17A content
Chapter 3: Selective targeting of PI3Kδ suppresses the function of human IL-17 producing T cells and innate lymphocytes: Relevance for IL-17 mediated diseases
Chapter 4: mTOR blockade by rapamycin in spondyloarthritis: Impact on inflammation and new bone formation in vitro and in vivo
Chapter 5: IL-17A and IL-17F expression and functional responses in rheumatoid arthritis and peripheral spondyloarthritis
Chapter 6
Chapter 7: Discussion
Nederlandse samenvatting (p. 214-217)
Nederlandse samenvatting (p. 218)
Conclusie; PhD portfolio; List of publications; Curriculum vitae; Dankwoord
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