Expression of PD-1 and Tim-3 is increased in skin of patients with bullous pemphigoid and pemphigus vulgaris.
Journal
Journal of the European Academy of Dermatology and Venereology : JEADV
ISSN: 1468-3083
Titre abrégé: J Eur Acad Dermatol Venereol
Pays: England
ID NLM: 9216037
Informations de publication
Date de publication:
Feb 2021
Feb 2021
Historique:
received:
26
02
2020
accepted:
08
06
2020
pubmed:
1
7
2020
medline:
15
5
2021
entrez:
30
6
2020
Statut:
ppublish
Résumé
Bullous pemphigoid (BP) and pemphigus vulgaris (PV) are common autoimmune bullous dermatoses (AIBD) characterized by blisters and erosions. Treatment options are limited and often insufficient. Immune checkpoint receptors play critical roles in immune homoeostasis and self- tolerance. Targeting checkpoint receptors is highly efficient in treatment of various cancers, but often also associated with autoimmune side effects. We therefore aimed to investigate the expression of immune checkpoint receptors in patients with BP and PV. We analysed expression of the checkpoint receptors programmed cell death protein 1 (PD-1), T-cell immunoglobulin and mucin domain 3 (Tim-3) and lymphocyte activation gene 3 (Lag-3) in lesional skin of patients with BP and PV compared to healthy control skin as well as the expression patterns of PD-1 and Tim-3 on various infiltrating immune cells in skin sections of AIBD by immunohistochemistry and immunofluorescence. We also measured serum levels of soluble PD-1, Tim-3 and Lag-3 in AIBD patients by ELISA. We report on increased expression of PD-1 and Tim-3, but not Lag-3, in lesional skin of patients with BP and PV. Investigating the expression pattern of PD-1 and Tim-3 on different cutaneous immune cells, we observed significant upregulation of PD-1 predominantly on infiltrating CD8 T cells and upregulation of Tim-3 on CD8 T cells as well as macrophages. Our results suggest exploring immune checkpoint receptors as novel therapeutic targets using an agonistic approach in autoimmune bullous diseases.
Sections du résumé
BACKGROUND
BACKGROUND
Bullous pemphigoid (BP) and pemphigus vulgaris (PV) are common autoimmune bullous dermatoses (AIBD) characterized by blisters and erosions. Treatment options are limited and often insufficient. Immune checkpoint receptors play critical roles in immune homoeostasis and self- tolerance. Targeting checkpoint receptors is highly efficient in treatment of various cancers, but often also associated with autoimmune side effects.
OBJECTIVES
OBJECTIVE
We therefore aimed to investigate the expression of immune checkpoint receptors in patients with BP and PV.
METHODS
METHODS
We analysed expression of the checkpoint receptors programmed cell death protein 1 (PD-1), T-cell immunoglobulin and mucin domain 3 (Tim-3) and lymphocyte activation gene 3 (Lag-3) in lesional skin of patients with BP and PV compared to healthy control skin as well as the expression patterns of PD-1 and Tim-3 on various infiltrating immune cells in skin sections of AIBD by immunohistochemistry and immunofluorescence. We also measured serum levels of soluble PD-1, Tim-3 and Lag-3 in AIBD patients by ELISA.
RESULTS
RESULTS
We report on increased expression of PD-1 and Tim-3, but not Lag-3, in lesional skin of patients with BP and PV. Investigating the expression pattern of PD-1 and Tim-3 on different cutaneous immune cells, we observed significant upregulation of PD-1 predominantly on infiltrating CD8 T cells and upregulation of Tim-3 on CD8 T cells as well as macrophages.
CONCLUSIONS
CONCLUSIONS
Our results suggest exploring immune checkpoint receptors as novel therapeutic targets using an agonistic approach in autoimmune bullous diseases.
Substances chimiques
HAVCR2 protein, human
0
Hepatitis A Virus Cellular Receptor 2
0
PDCD1 protein, human
0
Programmed Cell Death 1 Receptor
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
486-492Subventions
Organisme : Clinical Research Unit 'Pemphigoid Diseases'
ID : KFO 303
Organisme : Excellence Cluster 'Precision Medicine in Chronic Inflammation'
ID : EXC 2167-390884018
Organisme : Medical Faculty of the University of Luebeck, Luebeck, Germany
Organisme : University of Basel, Basel, Switzerland
Organisme : German Research Council (Research Training Group 'Modulation of Autoimmunity')
ID : GRK 1727
Informations de copyright
© 2020 European Academy of Dermatology and Venereology.
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