Novel mechanisms of T-cell and dendritic cell activation revealed by profiling of psoriasis on the 63,100-element oligonucleotide array.
A global picture of gene expression in the common immune-mediated skin disease, psoriasis, was obtained by interrogating the full set of Affymetrix GeneChips with psoriatic and control skin samples. We identified 1,338 genes with potential roles in psoriasis pathogenesis/maintenance and revealed many perturbed biological processes. A novel method for identifying transcription factor binding sites was also developed and applied to this dataset. Many of the identified sites are known to be involved in immune response and proliferation. An in-depth study of immune system genes revealed the presence of many regulating cytokines and chemokines within involved skin, and markers of dendritic cell (DC) activation in uninvolved skin. The combination of many CCR7+ T cells, DCs, and regulating chemokines in psoriatic lesions, together with the detection of DC activation markers in nonlesional skin, strongly suggests that the spatial organization of T cells and DCs could sustain chronic T-cell activation and persistence within focal skin regions.
Zhou
Xianghong
X
Department of Biostatistics, Harvard University, Boston 02115, USA.
Krueger
James G
JG
Kao
Ming-Chih J
MC
Lee
Ed
E
Du
Fenghe
F
Menter
Alan
A
Wong
Wing Hung
WH
Bowcock
Anne M
AM
D002469:Cell Separation; D016000:Cluster Analysis; D003713:Dendritic Cells / Q000502:physiology*; D005260:Female; D005434:Flow Cytometry / Q000379:methods / Q000706:statistics & numerical data; D020869:Gene Expression Profiling / Q000379:methods* / Q000706:statistics & numerical data; D006801:Humans; D008213:Lymphocyte Activation / Q000235:genetics*; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods* / Q000706:statistics & numerical data; D011565:Psoriasis / Q000235:genetics* / Q000276:immunology* / Q000503:physiopathology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology / Q000502:physiology; D013601:T-Lymphocytes / Q000502:physiology*