PD1 pathway in immune-mediated myopathies: Pathogenesis of dysfunctional T cells revisited.
Adolescent
Adult
Aged
Aged, 80 and over
Autoimmune Diseases
/ immunology
B7-H1 Antigen
Child, Preschool
Female
Humans
Male
Middle Aged
Muscle, Skeletal
/ pathology
Myositis
/ immunology
Myositis, Inclusion Body
/ immunology
Programmed Cell Death 1 Ligand 2 Protein
Programmed Cell Death 1 Receptor
T-Lymphocytes
Young Adult
Journal
Neurology(R) neuroimmunology & neuroinflammation
ISSN: 2332-7812
Titre abrégé: Neurol Neuroimmunol Neuroinflamm
Pays: United States
ID NLM: 101636388
Informations de publication
Date de publication:
05 2019
05 2019
Historique:
received:
07
09
2018
accepted:
23
01
2019
entrez:
3
5
2019
pubmed:
3
5
2019
medline:
3
5
2019
Statut:
epublish
Résumé
To investigate the relevance of dysfunctional T cells in immune-mediated myopathies. We analyzed T-cell exhaustion and senescence, in the context of programmed cell death protein 1 (PD1)-related immunity in skeletal muscle biopsies from patients with immune-mediated necrotizing myopathy (IMNM), sporadic inclusion body myositis (sIBM), and myositis induced by immune checkpoint inhibitors (irMyositis). Skeletal muscle biopsies from 12 patients with IMNM, 7 patients with sIBM, and 8 patients with irMyositis were analyzed by immunostaining and immunofluorescence as well as by quantitative PCR. Eight biopsies from nondisease participants served as controls. CD3 Persistent exposure to antigens in IMNMs and sIBM may lead to T-cell exhaustion, a process controlled by the PD1 receptor and its cognate ligands PD-L1/PD-L2. To our knowledge, these data are the first evidence of presence of dysfunctional T cells and relevance of the PD1 pathway in IMNM, sIBM, and irMyositis. These findings may guide the way to a novel understanding of the immune pathogenesis of immune-mediated myopathies.
Identifiants
pubmed: 31044146
doi: 10.1212/NXI.0000000000000558
pii: NEURIMMINFL2018018507
pmc: PMC6467687
doi:
Substances chimiques
B7-H1 Antigen
0
CD274 protein, human
0
PDCD1 protein, human
0
PDCD1LG2 protein, human
0
Programmed Cell Death 1 Ligand 2 Protein
0
Programmed Cell Death 1 Receptor
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e558Références
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