Cross-Disease Transcriptomics: Unique IL-17A Signaling in Psoriasis Lesions and an Autoimmune PBMC Signature

William R. Swindell, Mrinal K. Sarkar, Yun Liang, Xianying Xing, Johann E. Gudjonsson

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

Transcriptome studies of psoriasis have identified robust changes in mRNA expression through large-scale analysis of patient cohorts. These studies, however, have analyzed all mRNA changes in aggregate, without distinguishing between disease-specific and nonspecific differentially expressed genes (DEGs). In this study, RNA-seq meta-analysis was used to identify (1) psoriasis-specific DEGs altered in few diseases besides psoriasis and (2) nonspecific DEGs similarly altered in many other skin conditions. We show that few cutaneous DEGs are psoriasis specific and that the two DEG classes differ in their cell type and cytokine associations. Psoriasis-specific DEGs are expressed by keratinocytes and induced by IL-17A, whereas nonspecific DEGs are expressed by inflammatory cells and induced by IFN-γ and tumor necrosis factor. Peripheral blood mononuclear cell-derived DEGs were more psoriasis specific than cutaneous DEGs. Nonetheless, peripheral blood mononuclear cell DEGs associated with major histocompatibility complex class I and natural killer cells were commonly downregulated in psoriasis and other autoimmune diseases (e.g., multiple sclerosis, sarcoidosis, and juvenile rheumatoid arthritis). These findings demonstrate “cross-disease” transcriptomics as an approach to gain insights into the cutaneous and noncutaneous psoriasis transcriptomes. This highlighted unique contributions of IL-17A to the cytokine network and uncovered a blood-based gene signature that links psoriasis to other diseases of autoimmunity.

Original languageEnglish (US)
Pages (from-to)1820-1830
Number of pages11
JournalJournal of Investigative Dermatology
Volume136
Issue number9
DOIs
StatePublished - Sep 1 2016
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Fingerprint

Dive into the research topics of 'Cross-Disease Transcriptomics: Unique IL-17A Signaling in Psoriasis Lesions and an Autoimmune PBMC Signature'. Together they form a unique fingerprint.

Cite this