Pathogenese der Psoriasis vulgaris

Schäkel, Knut; Schön, Michael P.; Ghoreschi, Kamran

doi:10.1007/s00105-016-3800-8

Cited by 18 publications

(17 citation statements)

References 82 publications

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“…IL-36RN is a natural antagonist of the IL-1 family cytokine IL-36 ( 21 ). The consequence of mutations within the IL36RN gene is an increased production of NF-κB-regulated messengers ( 3 , 22 ). IL-36 is also relevant for clonal responses of Th17 cells in patients with generalized pustular psoriasis ( 23 ).…”

Section: On the Brink Of Understanding: The Link Between Genetics Andmentioning

confidence: 99%

The Interleukin-23/Interleukin-17 Axis Links Adaptive and Innate Immunity in Psoriasis

2018

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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.

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Section: On the Brink Of Understanding: The Link Between Genetics Andmentioning

confidence: 99%

The Interleukin-23/Interleukin-17 Axis Links Adaptive and Innate Immunity in Psoriasis

2018

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“…This positive feedback loop between Th17 cells and keratinocytes has been proved to contribute to the chronic inflammatory phase of psoriasis ( 43 , 49 , 50 ). Other proinflammatory factors released by pathogenic Th17 cells, such as IL-22, TNF-α, and granulocyte-macrophage colony-stimulating factor (GM-CSF), stimulate keratinocytes to release chemokines, further sustaining the inflammatory cycle to promote the development of psoriasis ( 51 , 52 ).…”

Section: The Main Role Of Pathogenic Th17 Cells In Psoriasismentioning

confidence: 99%

Transcription Factor Retinoid-Related Orphan Receptor γt: A Promising Target for the Treatment of Psoriasis

et al. 2018

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Psoriasis, which is a common chronic inflammatory skin disease, endangers human health and brings about a major economic burden worldwide. To date, treatments for psoriasis remain unsatisfied because of their clinical limitations and various side effects. Thus, developing a safer and more effective therapy for psoriasis is compelling. Previous studies have explicitly shown that psoriasis is an autoimmune disease that is predominantly mediated by T helper 17 (Th17) cells, which express high levels of interleukin-17 (IL-17) in response to interleukin-23 (IL-23). The discovery of the IL-23–Th17–IL-17 axis in the development of psoriasis has led to the paradigm shift of understanding pathogenesis of psoriasis. Although anti-IL-17 antibodies show marked clinical efficacy in treating psoriasis, compared with antibodies targeting IL-17A or IL-17R alone, targeting Th17 cells themselves may have a maximal benefit by affecting multiple proinflammatory cytokines, including IL-17A, IL-17F, IL-22, and granulocyte-macrophage colony-stimulating factor, which likely act synergistically to drive skin inflammation in psoriasis. In this review, we mainly focus on the critical role of Th17 cells in the pathogenesis of psoriasis. Especially, we explore the small molecules that target retinoid-related orphan receptor γt (RORγt), a vital transcription factor for Th17 cells. Given that RORγt is the lineage-defining transcription factor for Th17 cell differentiation, targeting RORγt via small molecular inverse agonists may be a promising strategy for the treatment of Th17-mediated psoriasis.

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“…Wir sind sehr dankbar, dass wir namhafte Expertinnen und Experten gewinnen konnten, die die Themenkomplexe von Pathogenese bis zu modernen Therapien verständlich beleuchten. So sind die wichtigsten Schritte der Psoriasispathogenese in dem Beitrag von Schäkel, Schön und Ghoreschi [1] dargestellt. Die Autoren beschreiben dabei nicht nur die in diesem Prozess beteiligten Zellen, sondern thematisieren auch die relevantesten Mediatoren zur Kommunikation dieser Zellen untereinander.…”

Section: Psoriasisunclassified