Cargando…

Deep Sequencing of the T-cell Receptor Repertoire Demonstrates Polyclonal T-cell Infiltrates in Psoriasis

It is well known that infiltration of pathogenic T-cells plays an important role in psoriasis pathogenesis. However, the antigen specificity of these activated T-cells is relatively unknown. Previous studies using T-cell receptor polymerase chain reaction technology (TCR-PCR) have suggested there ar...

Descripción completa

Detalles Bibliográficos
Autores principales: Harden, Jamie L., Hamm, David, Gulati, Nicholas, Lowes, Michelle A., Krueger, James G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: F1000Research 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4648215/
https://www.ncbi.nlm.nih.gov/pubmed/26594339
http://dx.doi.org/10.12688/f1000research.6756.1
_version_ 1782401212908306432
author Harden, Jamie L.
Hamm, David
Gulati, Nicholas
Lowes, Michelle A.
Krueger, James G.
author_facet Harden, Jamie L.
Hamm, David
Gulati, Nicholas
Lowes, Michelle A.
Krueger, James G.
author_sort Harden, Jamie L.
collection PubMed
description It is well known that infiltration of pathogenic T-cells plays an important role in psoriasis pathogenesis. However, the antigen specificity of these activated T-cells is relatively unknown. Previous studies using T-cell receptor polymerase chain reaction technology (TCR-PCR) have suggested there are expanded T-cell receptor (TCR) clones in psoriatic skin, suggesting a response to an unknown psoriatic antigen. Here we describe the results of high-throughput deep sequencing of the entire αβ- and γδ- TCR repertoire in normal healthy skin and psoriatic lesional and non-lesional skin. From this study, we were able to determine that there is a significant increase in the abundance of unique β- and γ- TCR sequences in psoriatic lesional skin compared to non-lesional and normal skin, and that the entire T-cell repertoire in psoriasis is polyclonal, with similar diversity to normal and non-lesional skin. Comparison of the αβ- and γδ- TCR repertoire in paired non-lesional and lesional samples showed many common clones within a patient, and these close were often equally abundant in non-lesional and lesional skin, again suggesting a diverse T-cell repertoire. Although there were similar (and low) amounts of shared β-chain sequences between different patient samples, there was significantly increased sequence sharing of the γ-chain in psoriatic skin from different individuals compared to those without psoriasis. This suggests that although the T-cell response in psoriasis is highly polyclonal, particular γδ- T-cell subsets may be associated with this disease. Overall, our findings present the feasibility of this technology to determine the entire αβ- and γδ- T-cell repertoire in skin, and that psoriasis contains polyclonal and diverse αβ- and γδ- T-cell populations.
format Online
Article
Text
id pubmed-4648215
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher F1000Research
record_format MEDLINE/PubMed
spelling pubmed-46482152015-11-20 Deep Sequencing of the T-cell Receptor Repertoire Demonstrates Polyclonal T-cell Infiltrates in Psoriasis Harden, Jamie L. Hamm, David Gulati, Nicholas Lowes, Michelle A. Krueger, James G. F1000Res Research Article It is well known that infiltration of pathogenic T-cells plays an important role in psoriasis pathogenesis. However, the antigen specificity of these activated T-cells is relatively unknown. Previous studies using T-cell receptor polymerase chain reaction technology (TCR-PCR) have suggested there are expanded T-cell receptor (TCR) clones in psoriatic skin, suggesting a response to an unknown psoriatic antigen. Here we describe the results of high-throughput deep sequencing of the entire αβ- and γδ- TCR repertoire in normal healthy skin and psoriatic lesional and non-lesional skin. From this study, we were able to determine that there is a significant increase in the abundance of unique β- and γ- TCR sequences in psoriatic lesional skin compared to non-lesional and normal skin, and that the entire T-cell repertoire in psoriasis is polyclonal, with similar diversity to normal and non-lesional skin. Comparison of the αβ- and γδ- TCR repertoire in paired non-lesional and lesional samples showed many common clones within a patient, and these close were often equally abundant in non-lesional and lesional skin, again suggesting a diverse T-cell repertoire. Although there were similar (and low) amounts of shared β-chain sequences between different patient samples, there was significantly increased sequence sharing of the γ-chain in psoriatic skin from different individuals compared to those without psoriasis. This suggests that although the T-cell response in psoriasis is highly polyclonal, particular γδ- T-cell subsets may be associated with this disease. Overall, our findings present the feasibility of this technology to determine the entire αβ- and γδ- T-cell repertoire in skin, and that psoriasis contains polyclonal and diverse αβ- and γδ- T-cell populations. F1000Research 2015-08-03 /pmc/articles/PMC4648215/ /pubmed/26594339 http://dx.doi.org/10.12688/f1000research.6756.1 Text en Copyright: © 2015 Harden JL et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Harden, Jamie L.
Hamm, David
Gulati, Nicholas
Lowes, Michelle A.
Krueger, James G.
Deep Sequencing of the T-cell Receptor Repertoire Demonstrates Polyclonal T-cell Infiltrates in Psoriasis
title Deep Sequencing of the T-cell Receptor Repertoire Demonstrates Polyclonal T-cell Infiltrates in Psoriasis
title_full Deep Sequencing of the T-cell Receptor Repertoire Demonstrates Polyclonal T-cell Infiltrates in Psoriasis
title_fullStr Deep Sequencing of the T-cell Receptor Repertoire Demonstrates Polyclonal T-cell Infiltrates in Psoriasis
title_full_unstemmed Deep Sequencing of the T-cell Receptor Repertoire Demonstrates Polyclonal T-cell Infiltrates in Psoriasis
title_short Deep Sequencing of the T-cell Receptor Repertoire Demonstrates Polyclonal T-cell Infiltrates in Psoriasis
title_sort deep sequencing of the t-cell receptor repertoire demonstrates polyclonal t-cell infiltrates in psoriasis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4648215/
https://www.ncbi.nlm.nih.gov/pubmed/26594339
http://dx.doi.org/10.12688/f1000research.6756.1
work_keys_str_mv AT hardenjamiel deepsequencingofthetcellreceptorrepertoiredemonstratespolyclonaltcellinfiltratesinpsoriasis
AT hammdavid deepsequencingofthetcellreceptorrepertoiredemonstratespolyclonaltcellinfiltratesinpsoriasis
AT gulatinicholas deepsequencingofthetcellreceptorrepertoiredemonstratespolyclonaltcellinfiltratesinpsoriasis
AT lowesmichellea deepsequencingofthetcellreceptorrepertoiredemonstratespolyclonaltcellinfiltratesinpsoriasis
AT kruegerjamesg deepsequencingofthetcellreceptorrepertoiredemonstratespolyclonaltcellinfiltratesinpsoriasis