Completed Digestion, Kidneys & Other Organs Infection & Immunity

Functional characterisation of the major susceptibility locus (PSORS1) for cutaneous inflammation in psoriasis

In plain English

AI plain-English summary

Psoriasis patients carry a specific genetic region, PSORS1, that dramatically raises their risk of developing the chronic skin condition, and this project will pinpoint exactly which genes in that region drive the inflammation. The problem is that current treatments manage symptoms but do not address the root cause. Researchers know that psoriasis involves a breakdown in the skin’s barrier function, a misfiring immune system, or both, but they do not understand the fundamental molecular defect that triggers the disease. Without that knowledge, developing preventive or curative therapies remains guesswork. If this work succeeds, it could identify the precise biological pathway that goes wrong in psoriasis. That would allow drug developers to target the cause rather than the symptoms, potentially leading to treatments that prevent flare-ups or even cure the condition. The economic and health burden of chronic inflammation—lifelong medication, doctor visits, lost productivity—could drop significantly. This is fundamental science: it characterises a genetic risk factor at the molecular level. Similar work on other autoimmune genes has led directly to new classes of drugs, such as biologics for rheumatoid arthritis.

View original technical description
Skin presents an essential barrier to environmental triggers capable of preventing challenge to the bodies natural defence mechanisms which includes a sophisticated immune surveillance network. Psoriasis, a life long skin disorder, is amongst a group of common conditions associated with chronic irritation and inflammation. Available evidence points to a fundamental defect in the capacity for barrier protection, dysregulation of the immune network or a combination of these through abnormal communication between skin and immune pathways. In order to develop new and effective therapies, a clear understanding of these processes and the fundamental defects that characterise the risk of developing psoriasis is now required. From a well defined region of the human genome, we have set out a series of studies designed to characterise the primary alterations that generate a very much increased risk disease development. Progress towards more effective ways to prevent or cure psoriasis would be expected to cut both in the short and long term, the heavy burden of chronic inflammation, and thus lead to a significant health and economic benefits compared to the present management of this disorder.

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Researchers

Adrian Hayday (Co-Investigator)Frank Nestle (Co-Investigator)Jonathan Barker (Co-Investigator)Richard Trembath (Principal Investigator)

Related Research

Grants with similar aims, by meaning.

Characterising the functional mechanisms of genetic risk loci for psoriasis
Functional role of HLA-C in Psoriasis
Processing and activation of IL-1 related cytokines in psoriatic inflammation.
Genetics analysis of Psoriasis: The GAP study.
An investigation of Langerhans cell function in psoriasis

Original classification

Research Grant

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