SHP-1 localization to the activating immune synapse promotes NK cell tolerance in MHC class I deficiency.

Détails

ID Serval
serval:BIB_F38A463DE9C1
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
SHP-1 localization to the activating immune synapse promotes NK cell tolerance in MHC class I deficiency.
Périodique
Science signaling
Auteur⸱e⸱s
Schmied L., Luu T.T., Søndergaard J.N., Hald S.H., Meinke S., Mohammad D.K., Singh S.B., Mayer C., Perinetti Casoni G., Chrobok M., Schlums H., Rota G., Truong H.M., Westerberg L.S., Guarda G., Alici E., Wagner A.K., Kadri N., Bryceson Y.T., Saeed M.B., Höglund P.
ISSN
1937-9145 (Electronic)
ISSN-L
1945-0877
Statut éditorial
Publié
Date de publication
11/04/2023
Peer-reviewed
Oui
Volume
16
Numéro
780
Pages
eabq0752
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Natural killer (NK) cells recognize virally infected cells and tumors. NK cell function depends on balanced signaling from activating receptors, recognizing products from tumors or viruses, and inhibitory receptors (such as KIR/Ly49), which recognize major histocompatibility complex class I (MHC-I) molecules. KIR/Ly49 signaling preserves tolerance to self but also conveys reactivity toward MHC-I-low target cells in a process known as NK cell education. Here, we found that NK cell tolerance and education were determined by the subcellular localization of the tyrosine phosphatase SHP-1. In mice lacking MHC-I molecules, uneducated, self-tolerant Ly49A <sup>+</sup> NK cells showed accumulation of SHP-1 in the activating immune synapse, where it colocalized with F-actin and the signaling adaptor protein SLP-76. Education of Ly49A <sup>+</sup> NK cells by the MHC-I molecule H2D <sup>d</sup> led to reduced synaptic accumulation of SHP-1, accompanied by augmented signaling from activating receptors. Education was also linked to reduced transcription of Ptpn6, which encodes SHP-1. Moreover, synaptic SHP-1 accumulation was reduced in NK cells carrying the H2D <sup>d</sup> -educated receptor Ly49G2 but not in those carrying the noneducating receptor Ly49I. Colocalization of Ly49A and SHP-1 outside of the synapse was more frequent in educated compared with uneducated NK cells, suggesting a role for Ly49A in preventing synaptic SHP-1 accumulation in NK cell education. Thus, distinct patterning of SHP-1 in the activating NK cell synapse may determine NK cell tolerance.
Mots-clé
Mice, Animals, Receptors, NK Cell Lectin-Like/metabolism, Antigens, Ly/metabolism, Killer Cells, Natural, Histocompatibility Antigens Class I/metabolism, Synapses/metabolism
Pubmed
Web of science
Création de la notice
17/04/2023 13:12
Dernière modification de la notice
17/11/2023 8:10
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