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231225s2021 xx |||||o 00| ||eng c |
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|a 10.1016/j.clim.2021.108802
|2 doi
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|a pubmed24n1094.xml
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|a (DE-627)NLM328430552
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|a (NLM)34298181
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|a (PII)S1521-6616(21)00139-X
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|a DE-627
|b ger
|c DE-627
|e rakwb
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|a eng
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| 100 |
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|a Desimio, Maria Giovanna
|e verfasserin
|4 aut
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| 245 |
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|a Altered NK-cell compartment and dysfunctional NKG2D/NKG2D-ligand axis in patients with ataxia-telangiectasia
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|c 2021
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| 336 |
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|a Text
|b txt
|2 rdacontent
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|a ƒaComputermedien
|b c
|2 rdamedia
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|a ƒa Online-Ressource
|b cr
|2 rdacarrier
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|a Date Completed 13.09.2021
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|a Date Revised 13.09.2021
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|a published: Print-Electronic
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|a Citation Status MEDLINE
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|a Copyright © 2021 Elsevier Inc. All rights reserved.
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|a Ataxia-telangiectasia (A-T) is a multisystem disorder caused by biallelic pathogenic variants in the gene encoding A-T mutated (ATM) kinase, a master regulator of the DNA damage response (DDR) pathway. Most A-T patients show cellular and/or humoral immunodeficiency that has been associated with cancer risk and reduced survival, but NK cells have not been thoroughly studied. Here we investigated NK cells of A-T patients with a special focus on the NKG2D receptor that triggers cytotoxicity upon engagement by its ligands (NKG2DLs) commonly induced via the DDR pathway on infected, transformed, and variously stressed cells. Using flow cytometry, we examined the phenotype and function of NK cells in 6 A-T patients as compared with healthy individuals. NKG2D expression was evaluated also by western blotting and RT-qPCR; plasma soluble NKG2DLs (sMICA, sMICB, sULBP1, ULBP2) were measured by ELISA. Results showed that A-T NK cells were skewed towards the CD56neg anergic phenotype and displayed decreased expression of NKG2D and perforin. NKG2D was reduced at the protein but not at the mRNA level and resulted in impaired NKG2D-mediated cytotoxicity in 4/6 A-T patients. Moreover, in A-T plasma we found 24-fold and 2-fold increase of sMICA and sULBP1, respectively, both inversely correlated with NKG2D expression. Overall, NK cells are disturbed in A-T patients showing reduced NKG2D expression, possibly caused by persistent engagement of its ligands, that may contribute to susceptibility to cancer and infections and represent novel targets for therapeutic interventions
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|a Journal Article
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|a Research Support, Non-U.S. Gov't
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|a ATM kinase
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|a Ataxia-telangiectasia
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|a Cytotoxicity
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| 650 |
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4 |
|a NKG2D
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4 |
|a Natural killer cells
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4 |
|a sMICA
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7 |
|a GPI-Linked Proteins
|2 NLM
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| 650 |
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|a Histocompatibility Antigens Class I
|2 NLM
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| 650 |
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|a Intercellular Signaling Peptides and Proteins
|2 NLM
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| 650 |
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7 |
|a Intracellular Signaling Peptides and Proteins
|2 NLM
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| 650 |
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|a KLRK1 protein, human
|2 NLM
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| 650 |
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7 |
|a Ligands
|2 NLM
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| 650 |
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7 |
|a MHC class I-related chain A
|2 NLM
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| 650 |
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7 |
|a MICB antigen
|2 NLM
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| 650 |
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7 |
|a NK Cell Lectin-Like Receptor Subfamily K
|2 NLM
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| 650 |
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7 |
|a RNA, Messenger
|2 NLM
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| 650 |
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|a ULBP1 protein, human
|2 NLM
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| 650 |
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|a ULBP2 protein, human
|2 NLM
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| 700 |
1 |
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|a Finocchi, Andrea
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Di Matteo, Gigliola
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Di Cesare, Silvia
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Giancotta, Carmela
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Conti, Francesca
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Chessa, Luciana
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Piane, Maria
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Montin, Davide
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Dellepiane, Marta
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Rossi, Paolo
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Cancrini, Caterina
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Doria, Margherita
|e verfasserin
|4 aut
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| 773 |
0 |
8 |
|i Enthalten in
|t Clinical immunology (Orlando, Fla.)
|d 1999
|g 230(2021) vom: 15. Sept., Seite 108802
|w (DE-627)NLM098196855
|x 1521-7035
|7 nnns
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| 773 |
1 |
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|g volume:230
|g year:2021
|g day:15
|g month:09
|g pages:108802
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| 856 |
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|u http://dx.doi.org/10.1016/j.clim.2021.108802
|3 Volltext
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|a SYSFLAG_A
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|a GBV_NLM
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|a GBV_ILN_11
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|a GBV_ILN_24
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|a GBV_ILN_350
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|a AR
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|d 230
|j 2021
|b 15
|c 09
|h 108802
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