TY - JOUR
T1 - Nonlesional atopic dermatitis skin shares similar T-cell clones with lesional tissues
AU - Brunner, P. M.
AU - Emerson, R. O.
AU - Tipton, C.
AU - Garcet, S.
AU - Khattri, S.
AU - Coats, I.
AU - Krueger, J. G.
AU - Guttman-Yassky, E.
N1 - Publisher Copyright:
© 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.
PY - 2017/12
Y1 - 2017/12
N2 - Background: Atopic dermatitis (AD) is characterized by robust immune activation. Various T-cell subsets, including Th2/Th22 cells, are increased in lesional and nonlesional skin. However, there is conflicting literature on the diversity of the T-cell receptor (TCR) repertoire in lesional AD, and its relation to nonlesional skin remains unclear. Methods: We performed high-throughput deep sequencing of the β-TCR repertoire in 29 lesional and 19 nonlesional AD biopsies, compared to six healthy control and six cutaneous T-cell lymphoma (CTCL) samples from previously published cohorts. Results: While greater T-cell infiltrates were observed in lesional vs nonlesional AD, TCR repertoire diversity was similar in lesional and nonlesional tissues, and absolute numbers of unique T-cell clones correlated with respective T-cell counts. Most (87%) top expanded lesional T-cell clones were shared with nonlesional tissues, and they were largely maintained after 16 weeks of successful treatment with topical triamcinolone. Nevertheless, both lesional and nonlesional AD showed a highly polyclonal TCR pattern, without evidence of oligoclonal expansion, or a preferred usage of certain V-β genes in AD skin. Size of the overall T-cell infiltrate, but not the level of clonality, correlated with mRNA levels of key inflammatory mediators (e.g., IL-13, CCL17, IL23p19, CXCL10). Conclusion: While AD harbors a highly polyclonal T-cell receptor repertoire, and despite the lack of information on TCR antigen specificity, the sharing of top abundant clones between lesional and nonlesional skin, and their persistence after months of therapy, points to the continuous presence of potentially pathogenic skin resident memory T cells well beyond clinically inflamed lesions.
AB - Background: Atopic dermatitis (AD) is characterized by robust immune activation. Various T-cell subsets, including Th2/Th22 cells, are increased in lesional and nonlesional skin. However, there is conflicting literature on the diversity of the T-cell receptor (TCR) repertoire in lesional AD, and its relation to nonlesional skin remains unclear. Methods: We performed high-throughput deep sequencing of the β-TCR repertoire in 29 lesional and 19 nonlesional AD biopsies, compared to six healthy control and six cutaneous T-cell lymphoma (CTCL) samples from previously published cohorts. Results: While greater T-cell infiltrates were observed in lesional vs nonlesional AD, TCR repertoire diversity was similar in lesional and nonlesional tissues, and absolute numbers of unique T-cell clones correlated with respective T-cell counts. Most (87%) top expanded lesional T-cell clones were shared with nonlesional tissues, and they were largely maintained after 16 weeks of successful treatment with topical triamcinolone. Nevertheless, both lesional and nonlesional AD showed a highly polyclonal TCR pattern, without evidence of oligoclonal expansion, or a preferred usage of certain V-β genes in AD skin. Size of the overall T-cell infiltrate, but not the level of clonality, correlated with mRNA levels of key inflammatory mediators (e.g., IL-13, CCL17, IL23p19, CXCL10). Conclusion: While AD harbors a highly polyclonal T-cell receptor repertoire, and despite the lack of information on TCR antigen specificity, the sharing of top abundant clones between lesional and nonlesional skin, and their persistence after months of therapy, points to the continuous presence of potentially pathogenic skin resident memory T cells well beyond clinically inflamed lesions.
KW - Atopic dermatitis
KW - T-cell receptor
KW - eczema
KW - nonlesional
KW - β-TCR repertoire
UR - http://www.scopus.com/inward/record.url?scp=85021389714&partnerID=8YFLogxK
U2 - 10.1111/all.13223
DO - 10.1111/all.13223
M3 - Article
C2 - 28599078
AN - SCOPUS:85021389714
SN - 0105-4538
VL - 72
SP - 2017
EP - 2025
JO - Allergy: European Journal of Allergy and Clinical Immunology
JF - Allergy: European Journal of Allergy and Clinical Immunology
IS - 12
ER -