SAP interacts with CD28 to inhibit PD-1 signaling in T lymphocytes.
Adult
Aged
Arthritis, Rheumatoid
/ genetics
Autoimmunity
/ genetics
CD28 Antigens
/ metabolism
Cell Line, Tumor
Female
Humans
Jurkat Cells
Male
Middle Aged
Phosphorylation
Programmed Cell Death 1 Receptor
/ antagonists & inhibitors
Signaling Lymphocytic Activation Molecule Associated Protein
/ genetics
T-Lymphocytes
/ immunology
Young Adult
CD28
DAS28
PD-1
Rheumatoid arthritis
SAP
Journal
Clinical immunology (Orlando, Fla.)
ISSN: 1521-7035
Titre abrégé: Clin Immunol
Pays: United States
ID NLM: 100883537
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
received:
01
10
2019
revised:
19
05
2020
accepted:
26
05
2020
pubmed:
7
6
2020
medline:
2
2
2021
entrez:
7
6
2020
Statut:
ppublish
Résumé
T cell co-stimulation is important for the maintenance of immunologic tolerance. Co-inhibitory receptors including programmed cell death-1 (PD-1) confer peripheral tolerance to prevent autoimmunity. SAP (SH2D1A) is an adaptor molecule that is important in T cell signaling and has been shown to interact with signaling lymphocytic activation molecule (SLAM) family receptors also in the context of self-tolerance. We recently reported that SAP interferes with PD-1 function. In the current study, we investigated the levels of SAP and PD-1 in patients with rheumatoid arthritis (RA) to further understand what role they play in disease activity. We observed increased SAP levels in lymphocytes of RA patients and found that PD-1 levels correlated positively with RA disease activity. Additionally, we found that SAP interacts with CD28 to inhibit T cell signaling in vitro. This work demonstrates a putative molecular mechanism for SAP mediated PD-1 inhibition.
Identifiants
pubmed: 32504780
pii: S1521-6616(19)30531-5
doi: 10.1016/j.clim.2020.108485
pmc: PMC9278890
mid: NIHMS1603825
pii:
doi:
Substances chimiques
CD28 Antigens
0
PDCD1 protein, human
0
Programmed Cell Death 1 Receptor
0
SH2D1A protein, human
0
Signaling Lymphocytic Activation Molecule Associated Protein
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
108485Subventions
Organisme : NIAID NIH HHS
ID : R01 AI125640
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI150597
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA231277
Pays : United States
Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that there are no competing interests.
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