Transcriptional landscape of psoriasis identifies the involvement of IL36 and IL36RN

被引:72
作者
Keermann, Maris [1 ,2 ]
Koeks, Sulev [3 ,4 ]
Reimann, Ene [3 ,4 ]
Prans, Ele [3 ,4 ]
Abram, Kristi [1 ,2 ]
Kingo, Kuelli [1 ,2 ]
机构
[1] Univ Tartu, Dept Dermatol, EE-50090 Tartu, Estonia
[2] Tartu Univ Hosp, Dept Dermatol, Tartu, Estonia
[3] Univ Tartu, Ctr Translat Med, Dept Pathophysiol, EE-50411 Tartu, Estonia
[4] Estonian Univ Life Sci, Dept Reprod Biol, Tartu, Estonia
来源
BMC GENOMICS | 2015年 / 16卷
关键词
Psoriasis; Transcriptome; Gene expression profiling; High-throughput nucleotide sequencing; Functional genomics; DIFFERENTIAL EXPRESSION ANALYSIS; GENE-EXPRESSION; RNA-SEQ; T-CELL; SKIN; ACTIVATION; MECHANISMS; INSIGHTS; TARGET; SERUM;
D O I
10.1186/s12864-015-1508-2
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Background: In present study we performed whole transcriptome analysis in plaque psoriasis patients and compared lesional skin with non-lesional skin and with the skin from healthy controls. We sequenced total RNA from 12 lesional (LP), 12 non-lesional (NLP) and from 12 normal (C) skin biopsies. Results: Compared with previous gene expression profiling studies we had three groups under analysis - LP, NLP and C. Using NLP samples allows to see the transcriptome of visually normal skin from psoriasis patient. In LP skin S100A12, S100A7A, LCE3E, DEFB4A, IL19 were found up regulated. In addition to already these well-described genes, we also found several other genes related to psoriasis. Namely, KLK9, OAS2, OAS3, PLA2G, IL36G, IL36RN were found to be significantly and consistently related to the psoriatic lesions and this finding is supported also by previous studies. The genes up-regulated in the LP samples were related to the innate immunity, IL17 and IL10 networks. In NLP samples innate immunity and IL17 network were activated, but activation of IL10 network was not evident. The transcriptional changes characteristic in the NLP samples can be considered as a molecular signature of "dormant psoriasis". Conclusions: Taken together, our study described the transcriptome profile characteristic for LP and NLP psoriatic skin. RNA profile of the NLP skin is in between the lesional and healthy skin, with its own specific pattern. We found that both LP and NLP have up-regulated IL17 network, whereas LP skin has up regulated IL10 related cytokines (IL19, IL20, IL24). Moreover, IL36G and IL36RN were identified as strong regulators of skin pathology in both LP and NLP skin samples, with stronger influence in LP samples.
引用
收藏
页数:11
相关论文
共 42 条
[1]   Transcriptome classification reveals molecular subtypes in psoriasis [J].
Ainali, Chrysanthi ;
Valeyev, Najl ;
Perera, Gayathri ;
Williams, Andrew ;
Gudjonsson, Johann E. ;
Ouzounis, Christos A. ;
Nestle, Frank O. ;
Tsoka, Sophia .
BMC GENOMICS, 2012, 13
[2]   IL-36γ/IL-1F9, an Innate T-bet Target in Myeloid Cells [J].
Bachmann, Malte ;
Scheiermann, Patrick ;
Haerdle, Lorena ;
Pfeilschifter, Josef ;
Muehl, Heiko .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2012, 287 (50) :41684-41696
[3]   SERUM INTERLEUKIN-6 LEVELS AS AN EARLY MARKER OF THERAPEUTIC RESPONSE TO UVB RADIATION AND TOPICAL STEROIDS IN PSORIATIC PATIENTS [J].
BONIFATI, C ;
SOLMONE, M ;
TRENTO, E ;
PIETRAVALLE, M ;
FAZIO, M ;
AMEGLIO, F .
INTERNATIONAL JOURNAL OF CLINICAL & LABORATORY RESEARCH, 1994, 24 (02) :122-123
[4]   Insights into psoriasis and other inflammatory diseases from large-scale gene expression studies [J].
Bowcock, AM ;
Shannon, W ;
Du, FH ;
Duncan, J ;
Cao, K ;
Aftergut, K ;
Catier, J ;
Fernandez-Vina, MA ;
Menter, A .
HUMAN MOLECULAR GENETICS, 2001, 10 (17) :1793-1805
[5]   IL-36γ (IL-1F9) Is a Biomarker for Psoriasis Skin Lesions [J].
D'Erme, Angelo Massimiliano ;
Wilsmann-Theis, Dagmar ;
Wagenpfeil, Julia ;
Hoelzel, Michael ;
Ferring-Schmitt, Sandra ;
Sternberg, Sonja ;
Wittmann, Miriam ;
Peters, Bettina ;
Bosio, Andreas ;
Bieber, Thomas ;
Wenzel, Joerg .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2015, 135 (04) :1025-1032
[6]   Interleukin-1 in the pathogenesis and treatment of inflammatory diseases [J].
Dinarello, Charles A. .
BLOOD, 2011, 117 (14) :3720-3732
[7]   The Interleukin-1 Family: Back to the Future [J].
Garlanda, Cecilia ;
Dinarello, Charles A. ;
Mantovani, Alberto .
IMMUNITY, 2013, 39 (06) :1003-1018
[8]   A T cell gene expression panel for the diagnosis and monitoring of disease activity in patients with systemic lupus erythematosus [J].
Grammatikos, Alexandros P. ;
Kyttaris, Vasileios C. ;
Kis-Toth, Katalin ;
Fitzgerald, Lisa M. ;
Devlin, Amy ;
Finnell, Michele D. ;
Tsokos, George C. .
CLINICAL IMMUNOLOGY, 2014, 150 (02) :192-200
[9]   Assessment of the Psoriatic Transcriptome in a Large Sample: Additional Regulated Genes and Comparisons with In Vitro Models [J].
Gudjonsson, Johann E. ;
Ding, Jun ;
Johnston, Andrew ;
Tejasvi, Trilokraj ;
Guzman, Andrew M. ;
Nair, Rajan P. ;
Voorhees, John J. ;
Abecasis, Goncalo R. ;
Elder, James T. .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2010, 130 (07) :1829-1840
[10]   Global Gene Expression Analysis Reveals Evidence for Decreased Lipid Biosynthesis and Increased Innate Immunity in Uninvolved Psoriatic Skin [J].
Gudjonsson, Johann E. ;
Ding, Jun ;
Li, Xing ;
Nair, Rajan P. ;
Tejasvi, Trilokraj ;
Qin, Zhaohui S. ;
Ghosh, Debashis ;
Aphale, Abhishek ;
Gumucio, Deborah L. ;
Voorhees, John J. ;
Abecasis, Goncalo R. ;
Elder, James T. .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2009, 129 (12) :2795-2804