Treg cell dysfunction and cutaneous exposure to S. aureus underlie eczema in DOCK8 deficiency.

DOCK8 deficiency Eczema S. aureus T regulatory cells

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:
05 Jan 2024
Historique:
received: 08 05 2023
revised: 19 12 2023
accepted: 27 12 2023
medline: 8 1 2024
pubmed: 8 1 2024
entrez: 7 1 2024
Statut: aheadofprint

Résumé

DOCK8-deficient patients have severe eczema, elevated IgE and eosinophilia, features of Atopic Dermatitis (AD). To understand the mechanisms of eczema in DOCK8 deficiency. Skin biopsies were characterized for histology, immuno-fluorescence microscopy, and gene expression. Skin barrier function was measured by trans-epidermal water loss. Allergic skin inflammation was elicited in mice by epicutaneous (EC) sensitization with ovalbumin (OVA) or cutaneous application of S. aureus. Skin lesions of DOCK8-deficient patients exhibited type-2 inflammation and the patients' skin was colonized by S. aureus, like in AD. Unlike in AD, DOCK8-deficient patients had a reduced FOXP3:CD4 ratio in their skin lesions, and their skin barrier function was intrinsically intact. Dock8

Sections du résumé

BACKGROUND BACKGROUND
DOCK8-deficient patients have severe eczema, elevated IgE and eosinophilia, features of Atopic Dermatitis (AD).
OBJECTIVE OBJECTIVE
To understand the mechanisms of eczema in DOCK8 deficiency.
METHODS METHODS
Skin biopsies were characterized for histology, immuno-fluorescence microscopy, and gene expression. Skin barrier function was measured by trans-epidermal water loss. Allergic skin inflammation was elicited in mice by epicutaneous (EC) sensitization with ovalbumin (OVA) or cutaneous application of S. aureus.
RESULTS RESULTS
Skin lesions of DOCK8-deficient patients exhibited type-2 inflammation and the patients' skin was colonized by S. aureus, like in AD. Unlike in AD, DOCK8-deficient patients had a reduced FOXP3:CD4 ratio in their skin lesions, and their skin barrier function was intrinsically intact. Dock8

Identifiants

DOI: 10.1016/j.jaci.2023.12.020 PMID: 38185418
pubmed: 38185418
pii: S0091-6749(24)00005-8
doi: 10.1016/j.jaci.2023.12.020
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024. Published by Elsevier Inc.

Auteurs

Hazel Wilkie (H)

Division of Immunology, Boston Children's Hospital and Department of Pediatrics Harvard Medical School, Boston, MA, USA.

Mrinmoy Das (M)

Division of Immunology, Boston Children's Hospital and Department of Pediatrics Harvard Medical School, Boston, MA, USA.

Tyler Pelovitz (T)

Division of Immunology, Boston Children's Hospital and Department of Pediatrics Harvard Medical School, Boston, MA, USA.

Wayne Bainter (W)

Division of Immunology, Boston Children's Hospital and Department of Pediatrics Harvard Medical School, Boston, MA, USA.

Brian Woods (B)

Division of Immunology, Boston Children's Hospital and Department of Pediatrics Harvard Medical School, Boston, MA, USA.

Mohammed Alasharee (M)

Division of Immunology, Boston Children's Hospital and Department of Pediatrics Harvard Medical School, Boston, MA, USA.

Ali Sobh (A)

Department of Pediatrics, Mansoura University Children's Hospital, Faculty of Medicine, Mansoura University, Egypt.

Safa Baris (S)

Division of Pediatric Allergy and Immunology, Marmara University, Istanbul, Turkey.

Sevgi Bilgic Eltan (SB)

Division of Pediatric Allergy and Immunology, Marmara University, Istanbul, Turkey.

Waleed Al-Herz (W)

Department of Pediatrics, Allergy and Clinical Immunology Unit, Al-Sabah Hospital, Kuwait City, Kuwait.

Mohamed-Ridha Barbouche (MR)

Department of Microbiology, Immunology and Infectious Diseases, College of Medicine and Medical Sciences, Arabian Gulf University, Manama, Bahrain.

Imen Ben-Mustapha (I)

Department of Immunology, Institut Pasteur de Tunis and University Tunis El-Manar, Tunis, Tunisia.

Meriem Ben-Ali (M)

Department of Immunology, Institut Pasteur de Tunis and University Tunis El-Manar, Tunis, Tunisia.

Mohamed T H Sallam (MTH)

Clinical Pathology Department, Faculty of Medicine, Ain Shams University.

Amany Awad (A)

Dermatology, Andrology, and STDs Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt.

Sohilla Lotfy (S)

Department of Pediatrics, Faculty of Medicine, Cairo University, Cairo, Egypt.

Aisha El Marsafy (A)

Department of Pediatrics, Faculty of Medicine, Cairo University, Cairo, Egypt.

Moushira Ezzelarab (M)

Department of Clinical and Chemical Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt.

Michael Farrar (M)

Center for Immunology, Masonic Cancer Center, Department of Laboratory and Pathology, University of Minnesota, Minneapolis, MN.

Brigitta A R Schmidt (BAR)

Department of Pathology, Boston Children's Hospital, Harvard Medical School, Boston, MA.

Monali NandyMazumdar (M)

Department of Dermatology and the Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY.

Emma Guttman-Yassky (E)

Department of Dermatology and the Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY.

Anthony Sheets (A)

Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.

Katie Maria Vidic (KM)

Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.

George Murphy (G)

Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.

Patrick M Schlievert (PM)

Department of Microbiology and Immunology, Carver College of Medicine, University of Iowa Health Care, Iowa City, IA.

Janet Chou (J)

Division of Immunology, Boston Children's Hospital and Department of Pediatrics Harvard Medical School, Boston, MA, USA.

Juan Manuel Leyva-Castillo (JM)

Division of Immunology, Boston Children's Hospital and Department of Pediatrics Harvard Medical School, Boston, MA, USA.

Erin Janssen (E)

Division of Immunology, Boston Children's Hospital and Department of Pediatrics Harvard Medical School, Boston, MA, USA.

Maheshwor Timilshina (M)

Division of Immunology, Boston Children's Hospital and Department of Pediatrics Harvard Medical School, Boston, MA, USA,. Electronic address: timelsena@gmail.com.

Raif S Geha (RS)

Division of Immunology, Boston Children's Hospital and Department of Pediatrics Harvard Medical School, Boston, MA, USA,. Electronic address: timelsena@gmail.com.

Classifications MeSH