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Differential Changes in Inflammatory Mononuclear Phagocyte and T-Cell Profiles within Psoriatic Skin during Treatment with Guselkumab vs. Secukinumab

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Differential Changes in Inflammatory Mononuclear Phagocyte and T-Cell Profiles within Psoriatic Skin during Treatment with Guselkumab vs. Secukinumab. / Mehta, Heena; Mashiko, Shunya; Angsana, Julianty; Rubio, Manuel; Hsieh, Ya-Ching M; Maari, Catherine; Reich, Kristian; Blauvelt, Andrew; Bissonnette, Robert; Muñoz-Elías, Ernesto J; Sarfati, Marika.

in: J INVEST DERMATOL, Jahrgang 141, Nr. 7, 07.2021, S. 1707-1718.e9.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Mehta, H, Mashiko, S, Angsana, J, Rubio, M, Hsieh, Y-CM, Maari, C, Reich, K, Blauvelt, A, Bissonnette, R, Muñoz-Elías, EJ & Sarfati, M 2021, 'Differential Changes in Inflammatory Mononuclear Phagocyte and T-Cell Profiles within Psoriatic Skin during Treatment with Guselkumab vs. Secukinumab', J INVEST DERMATOL, Jg. 141, Nr. 7, S. 1707-1718.e9. https://doi.org/10.1016/j.jid.2021.01.005

APA

Mehta, H., Mashiko, S., Angsana, J., Rubio, M., Hsieh, Y-C. M., Maari, C., Reich, K., Blauvelt, A., Bissonnette, R., Muñoz-Elías, E. J., & Sarfati, M. (2021). Differential Changes in Inflammatory Mononuclear Phagocyte and T-Cell Profiles within Psoriatic Skin during Treatment with Guselkumab vs. Secukinumab. J INVEST DERMATOL, 141(7), 1707-1718.e9. https://doi.org/10.1016/j.jid.2021.01.005

Vancouver

Mehta H, Mashiko S, Angsana J, Rubio M, Hsieh Y-CM, Maari C et al. Differential Changes in Inflammatory Mononuclear Phagocyte and T-Cell Profiles within Psoriatic Skin during Treatment with Guselkumab vs. Secukinumab. J INVEST DERMATOL. 2021 Jul;141(7):1707-1718.e9. https://doi.org/10.1016/j.jid.2021.01.005

Bibtex

@article{986818f0bd39457fbad61adb0e23a836,
title = "Differential Changes in Inflammatory Mononuclear Phagocyte and T-Cell Profiles within Psoriatic Skin during Treatment with Guselkumab vs. Secukinumab",
abstract = "Cellular sources of IL-23 and IL-17A driving skin inflammation in psoriasis remain unclear. Using high-dimensional unsupervised flow cytometry analysis, mononuclear phagocytes and T cells were examined in the same lesions of patients before and during guselkumab (IL-23p19 blocker) or secukinumab (IL-17A blocker) treatment. Among CD11c+HLA-DR+ mononuclear phagocytes, CD64brightCD163-CD14brightCD1c-CD1a‒ inflammatory monocyte‒like cells were the predominant IL-23-producing cells and, together with CD64-CD163-CD14-IL-23p19-TNF-α+ inflammatory dendritic cell‒like cells, were increased in lesional compared with those in nonlesional skin taken from the same patient. Within T cells, CD8+CD49a+ and/or CD103+ tissue-resident memory T cells, CD4+CD25+FoxP3+ regulatory T cells, and CD4+CD49a-CD103- T cells were increased. Moreover, CD4+CD49a-CD103- T cells and the relatively rare CD8+ memory T cells equally contributed to IL-17A production. Both treatments decreased the frequencies of inflammatory monocyte‒like, inflammatory dendritic cell‒like, and CD4+CD49a-CD103- T cells. In contrast, guselkumab reduced memory T cells while maintaining regulatory T cells and vice versa for secukinumab. Neither drug modified the frequencies of IL-17A+IL‒17F+/- CD4+ or CD8+ T cells. This study reveals the identity of the major IL-23+ mononuclear phagocyte and IL-17+ T-cell subsets in psoriatic skin lesions and paves the way for a better understanding of the mode of action of drugs targeting the IL-23/IL-17A pathway in psoriasis.",
keywords = "Adult, Aged, Antibodies, Monoclonal, Humanized/pharmacology, Cell Separation, Female, Flow Cytometry, Humans, Male, Middle Aged, Monocytes/drug effects, Psoriasis/drug therapy, Skin/cytology, T-Lymphocyte Subsets/drug effects, Young Adult",
author = "Heena Mehta and Shunya Mashiko and Julianty Angsana and Manuel Rubio and Hsieh, {Ya-Ching M} and Catherine Maari and Kristian Reich and Andrew Blauvelt and Robert Bissonnette and Mu{\~n}oz-El{\'i}as, {Ernesto J} and Marika Sarfati",
note = "Copyright {\textcopyright} 2021 The Authors. Published by Elsevier Inc. All rights reserved.",
year = "2021",
month = jul,
doi = "10.1016/j.jid.2021.01.005",
language = "English",
volume = "141",
pages = "1707--1718.e9",
journal = "J INVEST DERMATOL",
issn = "0022-202X",
publisher = "NATURE PUBLISHING GROUP",
number = "7",

}

RIS

TY - JOUR

T1 - Differential Changes in Inflammatory Mononuclear Phagocyte and T-Cell Profiles within Psoriatic Skin during Treatment with Guselkumab vs. Secukinumab

AU - Mehta, Heena

AU - Mashiko, Shunya

AU - Angsana, Julianty

AU - Rubio, Manuel

AU - Hsieh, Ya-Ching M

AU - Maari, Catherine

AU - Reich, Kristian

AU - Blauvelt, Andrew

AU - Bissonnette, Robert

AU - Muñoz-Elías, Ernesto J

AU - Sarfati, Marika

N1 - Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

PY - 2021/7

Y1 - 2021/7

N2 - Cellular sources of IL-23 and IL-17A driving skin inflammation in psoriasis remain unclear. Using high-dimensional unsupervised flow cytometry analysis, mononuclear phagocytes and T cells were examined in the same lesions of patients before and during guselkumab (IL-23p19 blocker) or secukinumab (IL-17A blocker) treatment. Among CD11c+HLA-DR+ mononuclear phagocytes, CD64brightCD163-CD14brightCD1c-CD1a‒ inflammatory monocyte‒like cells were the predominant IL-23-producing cells and, together with CD64-CD163-CD14-IL-23p19-TNF-α+ inflammatory dendritic cell‒like cells, were increased in lesional compared with those in nonlesional skin taken from the same patient. Within T cells, CD8+CD49a+ and/or CD103+ tissue-resident memory T cells, CD4+CD25+FoxP3+ regulatory T cells, and CD4+CD49a-CD103- T cells were increased. Moreover, CD4+CD49a-CD103- T cells and the relatively rare CD8+ memory T cells equally contributed to IL-17A production. Both treatments decreased the frequencies of inflammatory monocyte‒like, inflammatory dendritic cell‒like, and CD4+CD49a-CD103- T cells. In contrast, guselkumab reduced memory T cells while maintaining regulatory T cells and vice versa for secukinumab. Neither drug modified the frequencies of IL-17A+IL‒17F+/- CD4+ or CD8+ T cells. This study reveals the identity of the major IL-23+ mononuclear phagocyte and IL-17+ T-cell subsets in psoriatic skin lesions and paves the way for a better understanding of the mode of action of drugs targeting the IL-23/IL-17A pathway in psoriasis.

AB - Cellular sources of IL-23 and IL-17A driving skin inflammation in psoriasis remain unclear. Using high-dimensional unsupervised flow cytometry analysis, mononuclear phagocytes and T cells were examined in the same lesions of patients before and during guselkumab (IL-23p19 blocker) or secukinumab (IL-17A blocker) treatment. Among CD11c+HLA-DR+ mononuclear phagocytes, CD64brightCD163-CD14brightCD1c-CD1a‒ inflammatory monocyte‒like cells were the predominant IL-23-producing cells and, together with CD64-CD163-CD14-IL-23p19-TNF-α+ inflammatory dendritic cell‒like cells, were increased in lesional compared with those in nonlesional skin taken from the same patient. Within T cells, CD8+CD49a+ and/or CD103+ tissue-resident memory T cells, CD4+CD25+FoxP3+ regulatory T cells, and CD4+CD49a-CD103- T cells were increased. Moreover, CD4+CD49a-CD103- T cells and the relatively rare CD8+ memory T cells equally contributed to IL-17A production. Both treatments decreased the frequencies of inflammatory monocyte‒like, inflammatory dendritic cell‒like, and CD4+CD49a-CD103- T cells. In contrast, guselkumab reduced memory T cells while maintaining regulatory T cells and vice versa for secukinumab. Neither drug modified the frequencies of IL-17A+IL‒17F+/- CD4+ or CD8+ T cells. This study reveals the identity of the major IL-23+ mononuclear phagocyte and IL-17+ T-cell subsets in psoriatic skin lesions and paves the way for a better understanding of the mode of action of drugs targeting the IL-23/IL-17A pathway in psoriasis.

KW - Adult

KW - Aged

KW - Antibodies, Monoclonal, Humanized/pharmacology

KW - Cell Separation

KW - Female

KW - Flow Cytometry

KW - Humans

KW - Male

KW - Middle Aged

KW - Monocytes/drug effects

KW - Psoriasis/drug therapy

KW - Skin/cytology

KW - T-Lymphocyte Subsets/drug effects

KW - Young Adult

U2 - 10.1016/j.jid.2021.01.005

DO - 10.1016/j.jid.2021.01.005

M3 - SCORING: Journal article

C2 - 33524368

VL - 141

SP - 1707-1718.e9

JO - J INVEST DERMATOL

JF - J INVEST DERMATOL

SN - 0022-202X

IS - 7

ER -