Sebaceous Gland Atrophy in Psoriasis: An Explanation for Psoriatic Alopecia?
In a transcriptome study of lesional psoriatic skin (PP) versus normal skin, we found a coexpressed gene module (N5) enriched 11.5-fold for lipid biosynthetic genes. We also observed fewer visible hairs in PP skin, compared with uninvolved nonlesional psoriatic skin or normal skin (P < 0.0001). To ask whether these findings might be due to abnormalities of the pilosebaceous unit, we carried out three-dimensional morphometric analysis of paired PP and nonlesional psoriatic skin biopsies. Sebaceous glands were markedly atrophic in PP versus nonlesional psoriatic skin (91% average reduction in volume, P = 0.031). Module N5 genes were strongly downregulated in PP versus normal skin (fold change < 0.25, 44.4-fold) and strongly upregulated in sebaceous hyperplasia (fold change > 4, 54.1-fold). The intersection of PP-downregulated and sebaceous hyperplasia-upregulated gene lists generated a gene expression signature consisting solely of module N5 genes, whose expression in PP versus normal skin was inversely correlated with the signature of IL17-stimulated keratinocytes. Despite loss of visible hairs, morphometry identified elongated follicles in PP versus nonlesional psoriatic skin (average 1.7 vs. 1.2 μm, P = 0.020). These results document sebaceous gland atrophy in nonscalp psoriasis, identify a cytokine-regulated set of sebaceous gland signature genes, and suggest that loss of visible hair in PP skin may result from abnormal sebaceous gland function.
Department of Dermatology, University of Michigan, Ann Arbor, Michigan, USA.
Laure
L
Rittié
Department of Dermatology, University of Michigan, Ann Arbor, Michigan, USA; Ann Arbor Veterans Affairs Hospital, Ann Arbor, Michigan, USA.
Trilokraj
T
Tejasvi
Department of Dermatology, University of Michigan, Ann Arbor, Michigan, USA; Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA.
Paul W
PW
Harms
Department of Dermatology, University of Michigan, Ann Arbor, Michigan, USA.
Xianying
X
Xing
Department of Dermatology, University of Michigan, Ann Arbor, Michigan, USA.
Rajan P
RP
Nair
Department of Dermatology, University of Michigan, Ann Arbor, Michigan, USA.
Johann E
JE
Gudjonsson
Department of Dermatology, University of Michigan, Ann Arbor, Michigan, USA.
William R
WR
Swindell
Department of Dermatology, University of Michigan, Ann Arbor, Michigan, USA; Ann Arbor Veterans Affairs Hospital, Ann Arbor, Michigan, USA. Electronic address: jelder@umich.edu.
James T
JT
Elder
D000328:Adult; D000505:Alopecia / Q000473:pathology* / Q000503:physiopathology; D001284:Atrophy / Q000175:diagnosis; D001707:Biopsy, Needle; D018797:Cell Cycle Proteins / Q000235:genetics*; D016207:Cytokines / Q000378:metabolism; D004268:DNA-Binding Proteins; D018450:Disease Progression; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics*; D011565:Psoriasis / Q000473:pathology* / Q000503:physiopathology; D016601:RNA-Binding Proteins; D012627:Sebaceous Glands / Q000473:pathology*; D012680:Sensitivity and Specificity; D046509:Tissue Culture Techniques; D059467:Transcriptome / Q000235:genetics
D018797:Cell Cycle Proteins; D016207:Cytokines; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; C400546:THOC1 protein, human