The T Helper 17 Lineage in Pulmonary Diseases : cytokine analysis in local and systemic inflammation

Already in 1986, Mosmann and Coffman introduced the concept of separate types of T helper cells, which was based on the distinct cytokine profiles that these key effector cells of the immune system produce when stimulated to differentiate. Cytokines are small proteins that are crucial in the induction of an inflammatory response in the body. Originally, two types of CD4+ T lymphocytes were described: type 1 helper T cells (Th1 cells) and type 2 helper T cells (Th2 cells). Th1 cells produce large quantities of interferon (IFN)γ, mediate autoimmunity and are essential for the defense against intracellular pathogens such as in tuberculosis. Th2 cells produce mainly interleukin (IL)-4, play a central role in asthma pathogenesis and are important in clearing parasitic infections. In recent years, CD4+ T cells were shown to produce proinflammatory cytokines that could not be classified according to this Th1-Th2 paradigm. IL-17 was the most prominent amongst these cytokines and CD4+ T cells that preferentially produce IL-17 but not IFNγ or IL-4 were named Th17 cells. The discovery of this novel subset of T helper cells that produces IL-17 and IL-22 has since provided crucial new insights into immunoregulation, host defense and the pathogenesis of many conditions including autoimmune diseases. However, most of the evidence for an essential role for Th17 cells has been generated in mouse models and data on the contribution of Th17 cells in human diseases, including pulmonary disorders, remains limited. A better understanding of the cytokine networks involving the Th17 lineage in human pulmonary infection and inflammation will ultimately lead to the development of more effective treatment options in pulmonary diseases. Analysis of the local compartment, i.e. the lungs, in humans is, however, practically and ethically challenging, since procedures involving bronchoscopy are invasive, not without risks and unpleasant for patients. Because of this, studies on the Th17 lineage in human pulmonary diseases are also directed to other compartments in the body, in particular peripheral blood and sputum. In this thesis we aimed to explore the involvement of the Th17 lineage in the context of innate and adaptive immune responses in different infectious and inflammatory pulmonary diseases.