T helper 17 cells and Regulatory T cells in Pulmonary Sarcoidosis : It takes two to tangle

Sarcoidosis is an intriguingly complex immunological disorder. It is characterized by the formation of non-necrotizing granulomas that are most commonly found in the mediastinal lymph nodes and lungs of patients. Gaps in knowledge on sarcoidosis disease etiology and determinants of disease course have thus far impeded rational decisions on ‘Who, When and How’ to treat. The mainstay of sarcoidosis therapy remains immunosuppressive, using relatively high doses of systemic prednisone. However, although often effective, corticosteroid treatment can be accompanied by severe side effects. Detailed insight in the immunological response occurring in pulmonary sarcoidosis patients can help find determinants of disease etiology and disease course, which can yield new therapeutic targets. Therefore, the first aim of this thesis is to further unravel the immune-related pathogenesis of pulmonary sarcoidosis. The second aim is to gain insight into current prednisone treatment, in order to optimize treatment strategies to reduce side effects and increase quality of life of pulmonary sarcoidosis patients.
Findings described in this thesis provide a new perspective on sarcoidosis pathogenesis, challenging long-held paradigms and exploring novel approaches to further unravel this immunological complex disease. Furthermore, a rationale is provided to evaluate the potential of certain existing therapies that are used in other autoimmune diseases for pulmonary sarcoidosis. Finally, results of this thesis lay a strong foundation for future studies that can help individualize sarcoidosis treatment and thereby increase pulmonary sarcoidosis-related quality of care and patient-related quality of life.