CD33 (Siglec-3) Inhibitory Function: Role in the NKG2D/DAP10 Activating Pathway
CD33 (siglec-3), a well-known target in leukemia therapy, is an inhibitory sialoadhesin expressed in human leukocytes of the myeloid lineage and some lymphoid subsets, including NK cells. It may constitute a control mechanism of the innate immune system; nevertheless, its role as an inhibitory recep...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2019-01-01
|
| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2019/6032141 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849683380326629376 |
|---|---|
| author | Trinidad Hernández-Caselles Rubén Corral-San Miguel Antonio José Ruiz-Alcaraz Pilar García-Peñarrubia |
| author_facet | Trinidad Hernández-Caselles Rubén Corral-San Miguel Antonio José Ruiz-Alcaraz Pilar García-Peñarrubia |
| author_sort | Trinidad Hernández-Caselles |
| collection | DOAJ |
| description | CD33 (siglec-3), a well-known target in leukemia therapy, is an inhibitory sialoadhesin expressed in human leukocytes of the myeloid lineage and some lymphoid subsets, including NK cells. It may constitute a control mechanism of the innate immune system; nevertheless, its role as an inhibitory receptor remains elusive. Using human NK cells as a cellular model, we analyzed CD33 inhibitory function upon different activating receptors. In high-cytotoxicity NKL cells, CD33 displayed a prominent inhibition on cytotoxicity triggered by the activating receptors NKG2D and, in a lower extent, 2B4, whereas it did not inhibit NKp46-induced cytotoxicity. NKp46 was partially inhibited by CD33 only when low-cytotoxicity NKL cells were tested. CD33 triggering did not inhibit IFN-γ secretion, contrasting with ILT-2 and CD94/NKG2A inhibitory receptors that inhibited cytotoxicity and IFN-γ secretion induced by all activating receptors tested. CD33-mediated inhibition of NKG2D-induced triggering involved Vav1 dephosphorylation. Our results support the role of CD33 as an inhibitory receptor preferentially regulating the NKG2D/DAP10 cytotoxic signaling pathway, which could be involved in self-tolerance and tumor and infected cell recognition. |
| format | Article |
| id | doaj-art-dca3b2434f034521abbc3cbfeaff4bca |
| institution | DOAJ |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-dca3b2434f034521abbc3cbfeaff4bca2025-08-20T03:23:55ZengWileyJournal of Immunology Research2314-88612314-71562019-01-01201910.1155/2019/60321416032141CD33 (Siglec-3) Inhibitory Function: Role in the NKG2D/DAP10 Activating PathwayTrinidad Hernández-Caselles0Rubén Corral-San Miguel1Antonio José Ruiz-Alcaraz2Pilar García-Peñarrubia3Departamento de Bioquímica, Biología Molecular B e Inmunología, Faculty of Medicine, IMIB-University of Murcia, Murcia, SpainDepartamento de Bioquímica, Biología Molecular B e Inmunología, Faculty of Medicine, IMIB-University of Murcia, Murcia, SpainDepartamento de Bioquímica, Biología Molecular B e Inmunología, Faculty of Medicine, IMIB-University of Murcia, Murcia, SpainDepartamento de Bioquímica, Biología Molecular B e Inmunología, Faculty of Medicine, IMIB-University of Murcia, Murcia, SpainCD33 (siglec-3), a well-known target in leukemia therapy, is an inhibitory sialoadhesin expressed in human leukocytes of the myeloid lineage and some lymphoid subsets, including NK cells. It may constitute a control mechanism of the innate immune system; nevertheless, its role as an inhibitory receptor remains elusive. Using human NK cells as a cellular model, we analyzed CD33 inhibitory function upon different activating receptors. In high-cytotoxicity NKL cells, CD33 displayed a prominent inhibition on cytotoxicity triggered by the activating receptors NKG2D and, in a lower extent, 2B4, whereas it did not inhibit NKp46-induced cytotoxicity. NKp46 was partially inhibited by CD33 only when low-cytotoxicity NKL cells were tested. CD33 triggering did not inhibit IFN-γ secretion, contrasting with ILT-2 and CD94/NKG2A inhibitory receptors that inhibited cytotoxicity and IFN-γ secretion induced by all activating receptors tested. CD33-mediated inhibition of NKG2D-induced triggering involved Vav1 dephosphorylation. Our results support the role of CD33 as an inhibitory receptor preferentially regulating the NKG2D/DAP10 cytotoxic signaling pathway, which could be involved in self-tolerance and tumor and infected cell recognition.http://dx.doi.org/10.1155/2019/6032141 |
| spellingShingle | Trinidad Hernández-Caselles Rubén Corral-San Miguel Antonio José Ruiz-Alcaraz Pilar García-Peñarrubia CD33 (Siglec-3) Inhibitory Function: Role in the NKG2D/DAP10 Activating Pathway Journal of Immunology Research |
| title | CD33 (Siglec-3) Inhibitory Function: Role in the NKG2D/DAP10 Activating Pathway |
| title_full | CD33 (Siglec-3) Inhibitory Function: Role in the NKG2D/DAP10 Activating Pathway |
| title_fullStr | CD33 (Siglec-3) Inhibitory Function: Role in the NKG2D/DAP10 Activating Pathway |
| title_full_unstemmed | CD33 (Siglec-3) Inhibitory Function: Role in the NKG2D/DAP10 Activating Pathway |
| title_short | CD33 (Siglec-3) Inhibitory Function: Role in the NKG2D/DAP10 Activating Pathway |
| title_sort | cd33 siglec 3 inhibitory function role in the nkg2d dap10 activating pathway |
| url | http://dx.doi.org/10.1155/2019/6032141 |
| work_keys_str_mv | AT trinidadhernandezcaselles cd33siglec3inhibitoryfunctionroleinthenkg2ddap10activatingpathway AT rubencorralsanmiguel cd33siglec3inhibitoryfunctionroleinthenkg2ddap10activatingpathway AT antoniojoseruizalcaraz cd33siglec3inhibitoryfunctionroleinthenkg2ddap10activatingpathway AT pilargarciapenarrubia cd33siglec3inhibitoryfunctionroleinthenkg2ddap10activatingpathway |