期刊
HUMAN MOLECULAR GENETICS
卷 22, 期 9, 页码 1807-1815出版社
OXFORD UNIV PRESS
DOI: 10.1093/hmg/ddt034
关键词
-
资金
- American Skin Association
- National Psoriasis Foundation
- Dermatology Foundation
- A. Alfred Taubman Medical Research Institute by the Frances and Kenneth Eisenberg Emerging Scholar Award
- National Institute of Health [K08AR060802, R01 AR04742, AR050511, AR054966]
- American Skin Association Research Scholar Award
- Ann Arbor Veterans Affairs Hospital
- Babcock Endowment Fund at the University Of Michigan Department Of Dermatology
The IL12B gene encodes the common p40 subunit of IL-12 and IL-23, cytokines with key roles in Th1 and Th17 biology, respectively, and genetic variation in this region significantly influences risk of psoriasis. Here, we demonstrate that a psoriasis-associated risk haplotype at the IL12B locus leads to increased expression of IL12B by monocytes and correlated with increased serum levels of IL-12, IFN- and the IFN- induced chemokine, CXCL10. In contrast, serum IL-23 levels were decreased in risk carriers when compared with non-carriers. We further demonstrate that IL-12 is increased in psoriatic skin and that risk carriers manifest a skewing of the inflammatory network toward stronger IFN- responses. Taken together, our data demonstrate that the risk variant in IL12B associates with its increased expression and predisposes to stronger Th1 polarization through deviation of the local inflammatory environment toward increased IL-12/IFN- at the expense of IL-23/IL-17 responses.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据