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RNA Sequencing Keloid Transcriptome Associates Keloids With Th2, Th1, Th17/Th22, and JAK3-Skewing.
- Source :
- Frontiers in Immunology; 11/23/2020, Vol. 11, pN.PAG-N.PAG, 11p
- Publication Year :
- 2020
-
Abstract
- Keloids are disfiguring, fibroproliferative growths and their pathogenesis remains unclear, inhibiting therapeutic development. Available treatment options have limited efficacy and harbor safety concerns. Thus, there is a great need to clarify keloid pathomechanisms that may lead to novel treatments. In this study, we aimed to elucidate the profile of lesional and non-lesional keloid skin compared to normal skin. We performed gene (RNAseq, qRT-PCR) and protein (immunohistochemistry) expression analyses on biopsy specimens obtained from lesional and non-lesional skin of African American (AA) keloid patients compared to healthy skin from AA controls. Fold-change≥2 and false-discovery rate (FDR)<0.05 was used to define significance. We found that lesional versus normal skin showed significant up-regulation of markers of T-cell activation/migration (ICOS, CCR7), Th2- (IL-4R, CCL11, TNFSF4/OX40L), Th1- (CXCL9/CXCL10/CXCL11), Th17/Th22- (CCL20, S100As) pathways, and JAK/STAT-signaling (JAK3) (false-discovery rate [FDR]<0.05). Non-lesional skin also exhibited similar trends. We observed increased cellular infiltrates in keloid tissues, including T-cells, dendritic cells, mast cells, as well as greater IL-4rα<superscript>+</superscript>, CCR9<superscript>+</superscript>, and periostin<superscript>+</superscript> immunostaining. In sum, comprehensive molecular profiling demonstrated that both lesional and non-lesional skin show significant immune alternations, and particularly Th2 and JAK3 expression. This advocates for the investigation of novel treatments targeting the Th2 axis and/or JAK/STAT-signaling in keloid patients. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 16643224
- Volume :
- 11
- Database :
- Complementary Index
- Journal :
- Frontiers in Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 147200877
- Full Text :
- https://doi.org/10.3389/fimmu.2020.597741