Genetics of psoriasis and vitiligo, focus on IL10 family cytokines

Abstract

Naha eksponeeritus keskkonnamõjudele ja geneetiline eelsoodumus võivad viia normaalse immuunvastuse ja geeniekspresiooni tasakaalust välja, mis omakorda võib viia psoriaasi ja vitiliigo kujunemiseni. Interleukiin(IL)-10 olulist rolli on näidatud mitmetes immuunreaktsioonides ning selle ebatavaline ekspressioon on ilmnenud mitmete autoimmuunhaiguste puhul. IL10 perekonna tsütokiinid on seotud epidermise funktsioonidega ja on seostatavad psoriaasi ja vitiliigoga. Assotsiatsiooniuuring tuvastas IL20RA geeni polümorfismide olulise seose psoriaasiga, ning IL19, IL20 ja IL24 polümorfismide võimaliku mõju palmoplantaarse pustuloosi vastuvõtlikkusele. Ekspressioonianalüüs näitas, et IL22 on oluliselt seotud vitiliigoga, eriti selle haiguse aktiivse staadiumi avaldumisega. Et IL22 on tsentraalne põletikuline tsütokiin ka psoriaasi puhul, toetavad meie tulemused hüpoteesi, et erinevatel immunoloogilise taustaga nahahaigustel on sarnane patogeneetiline mehhanism.

Being exposed to a wide variety of environmental agents, the skin is prone to the development of autoimmune conditions, such as psoriasis and vitiligo. Failure to maintain epigenetic homeostasis in the immune response due to factors including environmental influences leads to aberrant gene expression, contributing to immune dysfunction and in some cases the development of autoimmunity in genetically predisposed individuals. Increasing evidence indicates that interleukin(IL)-10 and the IL10 family cytokines are involved in the function of epidermis and psoriasis. The aim of this research was to continue scientific investigation on the IL10 family genes and receptors in psoriasis vulgaris, and extend research to other cutaneous illnesses, like palmoplantar pustulosis and vitiligo. Studies of allelic variations revealed significant association between the IL20RA gene and psoriasis, and possible influence of the IL19, IL20 and IL24 genes in susceptibility to palmoplantar pustulosis. Studies of mRNA expression and protein level showed significant association of IL22 with vitiligo. Since IL22 appears to be a central cytokine mediating inflammatory responses, our data supports a hypothesis that different autoimmune skin diseases, such as psoriasis and vitiligo, may have similar pathogenic mechanisms.