Single-cell analysis implicates T


Journal

The Journal of allergy and clinical immunology
ISSN: 1097-6825
Titre abrégé: J Allergy Clin Immunol
Pays: United States
ID NLM: 1275002

Informations de publication

Date de publication:
10 2022
Historique:
received: 20 10 2021
revised: 04 03 2022
accepted: 20 04 2022
pubmed: 15 5 2022
medline: 12 10 2022
entrez: 14 5 2022
Statut: ppublish

Résumé

Palmoplantar pustulosis (PPP) is a severe inflammatory skin disorder characterized by eruptions of painful, neutrophil-filled pustules on the palms and soles. Although PPP has a profound effect on quality of life, it remains poorly understood and notoriously difficult to treat. We sought to investigate the immune pathways that underlie the pathogenesis of PPP. We applied bulk and single-cell RNA sequencing (RNA-Seq) methods to the analysis of skin biopsy samples and peripheral blood mononuclear cells. We validated our results by flow cytometry and immune fluorescence microscopy RESULTS: Bulk RNA-Seq of patient skin detected an unexpected signature of T-cell activation, with a significant overexpression of several T PPP is associated with complex T-cell activation patterns and may explain why biologic drugs that target individual T helper cell populations have shown limited therapeutic efficacy.

Sections du résumé

BACKGROUND
Palmoplantar pustulosis (PPP) is a severe inflammatory skin disorder characterized by eruptions of painful, neutrophil-filled pustules on the palms and soles. Although PPP has a profound effect on quality of life, it remains poorly understood and notoriously difficult to treat.
OBJECTIVE
We sought to investigate the immune pathways that underlie the pathogenesis of PPP.
METHODS
We applied bulk and single-cell RNA sequencing (RNA-Seq) methods to the analysis of skin biopsy samples and peripheral blood mononuclear cells. We validated our results by flow cytometry and immune fluorescence microscopy RESULTS: Bulk RNA-Seq of patient skin detected an unexpected signature of T-cell activation, with a significant overexpression of several T
CONCLUSIONS
PPP is associated with complex T-cell activation patterns and may explain why biologic drugs that target individual T helper cell populations have shown limited therapeutic efficacy.

Identifiants

pubmed: 35568077
pii: S0091-6749(22)00624-8
doi: 10.1016/j.jaci.2022.04.027
pii:
doi:

Substances chimiques

Biological Products 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

882-893

Subventions

Organisme : Medical Research Council
ID : MR/R015643/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/T02383X/1
Pays : United Kingdom

Informations de copyright

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Auteurs

Daniel McCluskey (D)

Department of Medical and Molecular Genetics, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom.

Natashia Benzian-Olsson (N)

Department of Medical and Molecular Genetics, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom.

Satveer K Mahil (SK)

St John's Institute of Dermatology, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom.

Niina Karoliina Hassi (NK)

Department of Medical and Molecular Genetics, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom.

Christian T Wohnhaas (CT)

Boehringer Ingelheim Pharma GmbH & Co KG, Biberach, Germany.

A David Burden (AD)

Institute of Infection Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom.

Christopher E M Griffiths (CEM)

Dermatology Centre, Salford Royal National Health Service (NHS) Foundation Trust, National Institute for Health Research (NIHR) Manchester Biomedical Research Centre, University of Manchester, Manchester, United Kingdom.

John R Ingram (JR)

Department of Dermatology, Division of Infection & Immunity, Cardiff University, Cardiff, United Kingdom.

Nick J Levell (NJ)

Norwich Medical School, University of East Anglia, Norwich, United Kingdom.

Richard Parslew (R)

Department of Dermatology, Royal Liverpool Hospitals, Liverpool, United Kingdom.

Andrew E Pink (AE)

St John's Institute of Dermatology, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom.

Nick J Reynolds (NJ)

Translational and Clinical Research Institute, Newcastle University and Department of Dermatology and NIHR Newcastle Biomedical Research Centre, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom.

Richard B Warren (RB)

Dermatology Centre, Salford Royal National Health Service (NHS) Foundation Trust, National Institute for Health Research (NIHR) Manchester Biomedical Research Centre, University of Manchester, Manchester, United Kingdom.

Sudha Visvanathan (S)

Boehringer Ingelheim Pharmaceuticals, Ridgefield, Conn.

Patrick Baum (P)

Boehringer Ingelheim Pharma GmbH & Co KG, Biberach, Germany.

Jonathan N Barker (JN)

St John's Institute of Dermatology, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom.

Catherine H Smith (CH)

St John's Institute of Dermatology, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom.

Francesca Capon (F)

Department of Medical and Molecular Genetics, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom. Electronic address: francesca.capon@kcl.ac.uk.

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