Meta-analysis of RNA sequencing datasets reveals an association between TRAJ23, psoriasis, and IL-17A

Alexander A. Merleev, Alina I. Marusina, Chelsea Ma, James T. Elder, Lam C. Tsoi, Siba P Raychaudhuri, Stephan Weidinger, Elizabeth A. Wang, Iannis Adamopoulos, Guillaume Luxardi, Johann E. Gudjonsson, Michiko Shimoda, Emanual Michael Maverakis

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Numerous studies of relatively few patients have linked T cell receptor (TCR) genes to psoriasis but have yielded dramatically conflicting results. To resolve these discrepancies, we have chosen to mine RNA-Seq datasets for patterns of TCR gene segment usage in psoriasis. A meta-analysis of 3 existing and 1 unpublished datasets revealed a statistically significant link between the relative expression of TRAJ23 and psoriasis and the psoriasis-associated cytokine IL-17A. TRGV5, a TCR-γ segment, was also associated with psoriasis but correlated instead with IL-36A, other IL-36 family members, and IL-17C (not IL-17A). In contrast, TRAJ39 was strongly associated with healthy skin. T cell diversity measurements and analysis of CDR3 sequences were also conducted, revealing no psoriasis-associated public CDR3 sequences. Finally, in comparison with the expression of TCR-αβ genes, the expression of TCR-γδ genes was relatively low but mildly elevated in psoriatic skin. These results have implications for the development of targeted therapies for psoriasis and other autoimmune diseases. Also, the techniques employed in this study have applications in other fields, such as cancer immunology and infectious disease.

Original languageEnglish (US)
JournalJCI insight
Volume3
Issue number13
DOIs
StatePublished - Jul 12 2018

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RNA Sequence Analysis
Interleukin-17
Psoriasis
Meta-Analysis
T-Cell Receptor Genes
Skin
T-Cell Antigen Receptor
Datasets
Allergy and Immunology
Autoimmune Diseases
Communicable Diseases
Sequence Analysis
RNA
Cytokines
T-Lymphocytes
Gene Expression

Keywords

  • Dermatology
  • Genetics
  • T cells

Cite this

Meta-analysis of RNA sequencing datasets reveals an association between TRAJ23, psoriasis, and IL-17A. / Merleev, Alexander A.; Marusina, Alina I.; Ma, Chelsea; Elder, James T.; Tsoi, Lam C.; Raychaudhuri, Siba P; Weidinger, Stephan; Wang, Elizabeth A.; Adamopoulos, Iannis; Luxardi, Guillaume; Gudjonsson, Johann E.; Shimoda, Michiko; Maverakis, Emanual Michael.

In: JCI insight, Vol. 3, No. 13, 12.07.2018.

Research output: Contribution to journalArticle

Merleev, Alexander A. ; Marusina, Alina I. ; Ma, Chelsea ; Elder, James T. ; Tsoi, Lam C. ; Raychaudhuri, Siba P ; Weidinger, Stephan ; Wang, Elizabeth A. ; Adamopoulos, Iannis ; Luxardi, Guillaume ; Gudjonsson, Johann E. ; Shimoda, Michiko ; Maverakis, Emanual Michael. / Meta-analysis of RNA sequencing datasets reveals an association between TRAJ23, psoriasis, and IL-17A. In: JCI insight. 2018 ; Vol. 3, No. 13.
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