Drug hypersensitivity and eosinophilia: The decisive role of p-i stimulation.
CD4/CD8 co-receptors
IL-5
TCR signalosome
drug hypersensitivity
eosinophilia
p-i concept
Journal
Allergy
ISSN: 1398-9995
Titre abrégé: Allergy
Pays: Denmark
ID NLM: 7804028
Informations de publication
Date de publication:
10 2023
10 2023
Historique:
revised:
31
05
2023
received:
29
03
2023
accepted:
16
06
2023
medline:
23
10
2023
pubmed:
3
7
2023
entrez:
3
7
2023
Statut:
ppublish
Résumé
Eosinophilia is a common finding in drug hypersensitivity reactions (DHR). Its cause is unclear, as neither antigen/allergen-driven inflammation nor clonal expansion is involved. Most delayed-DHRs are due to p-i (pharmacologic interaction of drugs with immune receptors). These are off-target activities of drugs with immune receptors that result in various types of T-cell stimulation, some of which involve excessive IL-5 production. Functional and phenotypic studies of T-cell clones and their TCR-transfected hybridoma cell lines revealed that some p-i-induced drug stimulations occur without CD4/ CD8 co-receptor engagement. The CD4/CD8 co-receptors link Lck (lymphocyte-specific protein tyrosine kinase) and LAT (linker for activation of T cells) to the TCR. Alteration of Lck or LAT can result in a TCR signalosome with enhanced IL-5 production. Thus, if a more affine TCR-[drug/peptide/HLA] interaction allows bypassing the CD4 co-receptor, a modified Lck/LAT activation may lead to a TCR signalosome with elevated IL-5 production. This "IL-5-TCR-signalosome" hypothesis could also explain eosinophilia in superantigen or allo-stimulation (graft-versus-host disease), in which evasion of CD4/CD8 co-receptors has also been described. It may open new therapeutic possibilities in certain eosinophilic diseases by directly targeting the IL-5-TCR signalosome.
Substances chimiques
Receptors, Antigen, T-Cell
0
Interleukin-5
0
CD8 Antigens
0
CD4 Antigens
0
Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
EC 2.7.10.2
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
2596-2605Informations de copyright
© 2023 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.
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