Abstract
Research into the pathophysiology of psoriasis has shed light onto many fascinating immunological interactions and underlying genetic constellations. Most prominent among these is the crosstalk between components of the innate and the adaptive immune system and the crucial role of interleukins (IL)-23 and -17 within this network. While it is clear that IL-23 drives and maintains the differentiation of Th17 lymphocytes, many aspects of the regulation of IL-23 and IL-17 are not quite as straightforward and have been unraveled only recently. For example, we know now that Th17 cells are not the only source of IL-17 but that cells of the innate immune system also produce considerable amounts of this central effector cytokine. In addition, there is IL-23-independent production of IL-17. Besides other innate immune cells, neutrophilic granulocytes prominently contribute to IL-17-related immune regulations in psoriasis, and it appears that they employ several mechanisms including the formation of neutrophil extracellular traps. Here, we strive to put the central role of the IL-23/IL-17 axis into perspective within the crosstalk between components of the innate and the adaptive immune system. Our aim is to better understand the complex immune regulation in psoriasis, a disorder that has become a model disease for chronic inflammation.
Highlights
Psoriasis has evolved into an instructive model disease for many immune-mediated disorders
They are key effector cells of the innate immune system and they target invading microbes by phagocytosis, the generation of reactive oxygen species (ROS), as well as the release of AMPs and inflammatory mediators. While these “classical” strategies are well known for many years, the recent discovery of neutrophil extracellular traps (NETs) has catapulted neutrophils back into the focus of immunological science including psoriasis research [112]
Similar to approaches used in rheumatoid arthritis, it can be speculated that blocking inflammatory mediators early on in the disease process could intercept the evolution of psoriasis toward a more detrimental systemic disease
Summary
Psoriasis has evolved into an instructive model disease for many immune-mediated disorders. Our increasing understanding of pathophysiological principles has facilitated the development of effective therapies. Perhaps important, such therapies have taught us a lot about disease mechanisms [1, 2]. Psoriasis-directed precision medicine illuminates vividly how pieces of the immunological mosaic fall into place to improve our patients’ lives. In this light, we here discuss immunological mechanisms governing the pathogenesis of psoriasis with a certain emphasis on links between the adaptive and the innate immune system. We believe that such interactive and dynamic links are of paramount importance for complex immune regulations in general and are key to successful therapeutic interventions
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