TY - JOUR
T1 - Cross-Disease Transcriptomics
T2 - Unique IL-17A Signaling in Psoriasis Lesions and an Autoimmune PBMC Signature
AU - Swindell, William R.
AU - Sarkar, Mrinal K.
AU - Liang, Yun
AU - Xing, Xianying
AU - Gudjonsson, Johann E.
N1 - Publisher Copyright:
© 2016 The Authors
PY - 2016/9/1
Y1 - 2016/9/1
N2 - 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.
AB - 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.
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U2 - 10.1016/j.jid.2016.04.035
DO - 10.1016/j.jid.2016.04.035
M3 - Article
C2 - 27206706
AN - SCOPUS:84992491178
SN - 0022-202X
VL - 136
SP - 1820
EP - 1830
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 9
ER -