Inherited SLP76 deficiency in humans causes severe combined immunodeficiency, neutrophil and platelet defects.
Adaptor Proteins, Signal Transducing
/ chemistry
Amino Acid Sequence
Base Sequence
Blood Platelets
/ metabolism
Fatal Outcome
Humans
Infant
Infant, Newborn
Jurkat Cells
Mutation
/ genetics
Neutrophils
/ metabolism
Phenotype
Phosphoproteins
/ chemistry
Receptors, Antigen, B-Cell
/ metabolism
Receptors, Antigen, T-Cell
/ metabolism
Severe Combined Immunodeficiency
/ immunology
Signal Transduction
Journal
The Journal of experimental medicine
ISSN: 1540-9538
Titre abrégé: J Exp Med
Pays: United States
ID NLM: 2985109R
Informations de publication
Date de publication:
01 03 2021
01 03 2021
Historique:
received:
24
05
2020
revised:
06
09
2020
accepted:
08
10
2020
entrez:
24
11
2020
pubmed:
25
11
2020
medline:
15
9
2021
Statut:
ppublish
Résumé
The T cell receptor (TCR) signaling pathway is an ensemble of numerous proteins that are crucial for an adequate immune response. Disruption of any protein involved in this pathway leads to severe immunodeficiency and unfavorable clinical outcomes. Here, we describe an infant with severe immunodeficiency who was found to have novel biallelic mutations in SLP76. SLP76 is a key protein involved in TCR signaling and in other hematopoietic pathways. Previous studies of this protein were performed using Jurkat-derived human leukemic T cell lines and SLP76-deficient mice. Our current study links this gene, for the first time, to a human immunodeficiency characterized by early-onset life-threatening infections, combined T and B cell immunodeficiency, severe neutrophil defects, and impaired platelet aggregation. Hereby, we characterized aspects of the patient's immune phenotype, modeled them with an SLP76-deficient Jurkat-derived T cell line, and rescued some consequences using ectopic expression of wild-type SLP76. Understanding human diseases due to SLP76 deficiency is helpful in explaining the mixed T cell and neutrophil defects, providing a guide for exploring human SLP76 biology.
Identifiants
pubmed: 33231617
pii: 211562
doi: 10.1084/jem.20201062
pmc: PMC7690938
pii:
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
Phosphoproteins
0
Receptors, Antigen, B-Cell
0
Receptors, Antigen, T-Cell
0
SLP-76 signal Transducing adaptor proteins
0
Types de publication
Case Reports
Journal Article
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2020 Lev et al.
Déclaration de conflit d'intérêts
Disclosures: The authors declare no competing interests exist.
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