CHARACTERIZATION OF B7H6, AN ENDOGENOUS LIGAND FOR THE NK CELL ACTIVATING RECEPTOR NKP30, REVEALS THE IDENTITY OF TWO DIFFERENT SOLUBLE ISOFORMS DURING NORMAL HUMAN PREGNANCY

B7H6, an endogenous ligand expressed on tumor cell surfaces, triggers NKp30-mediated activation of human NK cells. In contrast, the release of soluble B7H6 has been proposed as a novel mechanism by which tumors might evade NK cell-mediatedrecognition. Since NK cells are critical for the maintenance...

Full description

Bibliographic Details
Authors: GUTIERREZ FRANCO, JORGE, BUENO TOPETE, MIRIAM RUTH, HARAMATI, JESSE, NAVARRO HERNANDEZ, ROSA ELENA, ESCARRA SENMARTI, MARTA, VEGA MAGAÑA, NATALI, DEL TORO ARREOLA, ALICIA, PEREIRA SUAREZ, ANA LAURA, DEL TORO ARREOLA, SUSANA, HERNANDEZ GUTIERREZ, RODOLFO
Format: article
Status:Published version
Publication Date:2018
Country:México
Institution:Universidad Autónoma de Nayarit
Repository:Repositorio Institucional Aramara de la UAN
Language:English
OAI Identifier:oai:dspace.uan.mx:123456789/1094
Online Access:http://dx.doi.org/10.1016/j.imbio.2017.10.012
http://dspace.uan.mx:8080/jspui/handle/123456789/1094
Access Level:Open access
Keyword:PregnancyB7H6NKp30NK cells
EmbarazoB7H6NKp30NK células
EMBRIOLOGÍA HUMANA [241006]
id MX_4ec070a8838ee5b04dbd6bb69863d8a6
oai_identifier_str oai:dspace.uan.mx:123456789/1094
network_acronym_str MX
network_name_str México
repository_id_str
dc.title.none.fl_str_mv CHARACTERIZATION OF B7H6, AN ENDOGENOUS LIGAND FOR THE NK CELL ACTIVATING RECEPTOR NKP30, REVEALS THE IDENTITY OF TWO DIFFERENT SOLUBLE ISOFORMS DURING NORMAL HUMAN PREGNANCY
title CHARACTERIZATION OF B7H6, AN ENDOGENOUS LIGAND FOR THE NK CELL ACTIVATING RECEPTOR NKP30, REVEALS THE IDENTITY OF TWO DIFFERENT SOLUBLE ISOFORMS DURING NORMAL HUMAN PREGNANCY
spellingShingle CHARACTERIZATION OF B7H6, AN ENDOGENOUS LIGAND FOR THE NK CELL ACTIVATING RECEPTOR NKP30, REVEALS THE IDENTITY OF TWO DIFFERENT SOLUBLE ISOFORMS DURING NORMAL HUMAN PREGNANCY
GUTIERREZ FRANCO, JORGE
PregnancyB7H6NKp30NK cells
EmbarazoB7H6NKp30NK células
EMBRIOLOGÍA HUMANA [241006]
title_short CHARACTERIZATION OF B7H6, AN ENDOGENOUS LIGAND FOR THE NK CELL ACTIVATING RECEPTOR NKP30, REVEALS THE IDENTITY OF TWO DIFFERENT SOLUBLE ISOFORMS DURING NORMAL HUMAN PREGNANCY
title_full CHARACTERIZATION OF B7H6, AN ENDOGENOUS LIGAND FOR THE NK CELL ACTIVATING RECEPTOR NKP30, REVEALS THE IDENTITY OF TWO DIFFERENT SOLUBLE ISOFORMS DURING NORMAL HUMAN PREGNANCY
title_fullStr CHARACTERIZATION OF B7H6, AN ENDOGENOUS LIGAND FOR THE NK CELL ACTIVATING RECEPTOR NKP30, REVEALS THE IDENTITY OF TWO DIFFERENT SOLUBLE ISOFORMS DURING NORMAL HUMAN PREGNANCY
title_full_unstemmed CHARACTERIZATION OF B7H6, AN ENDOGENOUS LIGAND FOR THE NK CELL ACTIVATING RECEPTOR NKP30, REVEALS THE IDENTITY OF TWO DIFFERENT SOLUBLE ISOFORMS DURING NORMAL HUMAN PREGNANCY
title_sort CHARACTERIZATION OF B7H6, AN ENDOGENOUS LIGAND FOR THE NK CELL ACTIVATING RECEPTOR NKP30, REVEALS THE IDENTITY OF TWO DIFFERENT SOLUBLE ISOFORMS DURING NORMAL HUMAN PREGNANCY
dc.creator.none.fl_str_mv GUTIERREZ FRANCO, JORGE
BUENO TOPETE, MIRIAM RUTH
HARAMATI, JESSE
NAVARRO HERNANDEZ, ROSA ELENA
ESCARRA SENMARTI, MARTA
VEGA MAGAÑA, NATALI
DEL TORO ARREOLA, ALICIA
PEREIRA SUAREZ, ANA LAURA
DEL TORO ARREOLA, SUSANA
HERNANDEZ GUTIERREZ, RODOLFO
author GUTIERREZ FRANCO, JORGE
author_facet GUTIERREZ FRANCO, JORGE
BUENO TOPETE, MIRIAM RUTH
HARAMATI, JESSE
NAVARRO HERNANDEZ, ROSA ELENA
ESCARRA SENMARTI, MARTA
VEGA MAGAÑA, NATALI
DEL TORO ARREOLA, ALICIA
PEREIRA SUAREZ, ANA LAURA
DEL TORO ARREOLA, SUSANA
HERNANDEZ GUTIERREZ, RODOLFO
author_role author
author2 BUENO TOPETE, MIRIAM RUTH
HARAMATI, JESSE
NAVARRO HERNANDEZ, ROSA ELENA
ESCARRA SENMARTI, MARTA
VEGA MAGAÑA, NATALI
DEL TORO ARREOLA, ALICIA
PEREIRA SUAREZ, ANA LAURA
DEL TORO ARREOLA, SUSANA
HERNANDEZ GUTIERREZ, RODOLFO
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv PregnancyB7H6NKp30NK cells
EmbarazoB7H6NKp30NK células
EMBRIOLOGÍA HUMANA [241006]
topic PregnancyB7H6NKp30NK cells
EmbarazoB7H6NKp30NK células
EMBRIOLOGÍA HUMANA [241006]
description B7H6, an endogenous ligand expressed on tumor cell surfaces, triggers NKp30-mediated activation of human NK cells. In contrast, the release of soluble B7H6 has been proposed as a novel mechanism by which tumors might evade NK cell-mediatedrecognition. Since NK cells are critical for the maintenance of early pregnancy, it is not illogical that soluble B7H6 might also be an important factor in directing NK cell activity during normal pregnancy. Thus, this study was focused on the characterization of soluble B7H6 during the development of normal pregnancy. Serum samples were obtained from healthy pregnant women who were experiencing their second pregnancies (n = 36). Additionally, 17 of these pregnant participants were longitudinally studied for the presence of B7H6 during their second and third trimesters. Age-matched healthy non-pregnant women served as controls (n = 30). The presence of soluble B7H6 was revealed by Western blotting. A further characterization was performed using an immunoproteomic approach b sed on 2DE-Western blotting combined with MALDI-MS. The results show that sera from all pregnant women were characterized by the presence of two novel isoforms of B7H6, both with lower MW than the reported of 51 kDa. These isoforms were either a heavy (∼37 kDa) or a light isoform (∼30 kDa) and were mutually exclusive. N-glycosylation did not completely explain the different molecular weights exhibited by the two isoforms, as was demonstrated by enzymatic deglycosylation with PNGase F. The confirmation of the identity and molecular mass of each isoform indicates that B7H6, while maintaining the C- and N-termini, is most likely released during pregnancy by a mechanism distinct from proteolytic cleavage. We found that both isoforms, but mainly the heavier B7H6, were released via exosomes; and that the lighter isoform was also released in an exosome-free manner that was not observed in the heavy isoform samples. In conclusion, we find that soluble B7H6 is constitutively expressed during pregnancy and that, moreover, the soluble B7H6 is present in two new isoforms, which are released by exosomal and exosome-free mechanisms.
publishDate 2018
dc.date.none.fl_str_mv 2018-10-04T20:11:59Z
2018-10-04T20:11:59Z
2018-01
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://dx.doi.org/10.1016/j.imbio.2017.10.012
0171-2985
http://dspace.uan.mx:8080/jspui/handle/123456789/1094
url http://dx.doi.org/10.1016/j.imbio.2017.10.012
http://dspace.uan.mx:8080/jspui/handle/123456789/1094
identifier_str_mv 0171-2985
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Público en general
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/cc-by-nc-sa
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/cc-by-nc-sa
dc.publisher.none.fl_str_mv Immunobiology
publisher.none.fl_str_mv Immunobiology
dc.source.none.fl_str_mv https://www.sciencedirect.com/science/article/pii/S017129851730147X
reponame:Repositorio Institucional Aramara de la UAN
instname:Universidad Autónoma de Nayarit
instacron:UAN
instname_str Universidad Autónoma de Nayarit
instacron_str UAN
institution UAN
reponame_str Repositorio Institucional Aramara de la UAN
collection Repositorio Institucional Aramara de la UAN
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1858175213617807360
spelling CHARACTERIZATION OF B7H6, AN ENDOGENOUS LIGAND FOR THE NK CELL ACTIVATING RECEPTOR NKP30, REVEALS THE IDENTITY OF TWO DIFFERENT SOLUBLE ISOFORMS DURING NORMAL HUMAN PREGNANCYGUTIERREZ FRANCO, JORGEBUENO TOPETE, MIRIAM RUTHHARAMATI, JESSENAVARRO HERNANDEZ, ROSA ELENAESCARRA SENMARTI, MARTAVEGA MAGAÑA, NATALIDEL TORO ARREOLA, ALICIAPEREIRA SUAREZ, ANA LAURADEL TORO ARREOLA, SUSANAHERNANDEZ GUTIERREZ, RODOLFOPregnancyB7H6NKp30NK cellsEmbarazoB7H6NKp30NK célulasEMBRIOLOGÍA HUMANA [241006]B7H6, an endogenous ligand expressed on tumor cell surfaces, triggers NKp30-mediated activation of human NK cells. In contrast, the release of soluble B7H6 has been proposed as a novel mechanism by which tumors might evade NK cell-mediatedrecognition. Since NK cells are critical for the maintenance of early pregnancy, it is not illogical that soluble B7H6 might also be an important factor in directing NK cell activity during normal pregnancy. Thus, this study was focused on the characterization of soluble B7H6 during the development of normal pregnancy. Serum samples were obtained from healthy pregnant women who were experiencing their second pregnancies (n = 36). Additionally, 17 of these pregnant participants were longitudinally studied for the presence of B7H6 during their second and third trimesters. Age-matched healthy non-pregnant women served as controls (n = 30). The presence of soluble B7H6 was revealed by Western blotting. A further characterization was performed using an immunoproteomic approach b sed on 2DE-Western blotting combined with MALDI-MS. The results show that sera from all pregnant women were characterized by the presence of two novel isoforms of B7H6, both with lower MW than the reported of 51 kDa. These isoforms were either a heavy (∼37 kDa) or a light isoform (∼30 kDa) and were mutually exclusive. N-glycosylation did not completely explain the different molecular weights exhibited by the two isoforms, as was demonstrated by enzymatic deglycosylation with PNGase F. The confirmation of the identity and molecular mass of each isoform indicates that B7H6, while maintaining the C- and N-termini, is most likely released during pregnancy by a mechanism distinct from proteolytic cleavage. We found that both isoforms, but mainly the heavier B7H6, were released via exosomes; and that the lighter isoform was also released in an exosome-free manner that was not observed in the heavy isoform samples. In conclusion, we find that soluble B7H6 is constitutively expressed during pregnancy and that, moreover, the soluble B7H6 is present in two new isoforms, which are released by exosomal and exosome-free mechanisms.B7H6, un ligando endógeno expresado en las superficies de las células tumorales, desencadena la activación mediada por NKp30 de células NK humanas. En contraste, la liberación de B7H6 soluble se ha propuesto como un nuevo mecanismo por el cual los tumores pueden evadir el reconocimiento mediado por células NK. Dado que las células NK son críticas para el mantenimiento del embarazo temprano, no es ilógico que el B7H6 soluble también pueda ser un factor importante para dirigir la actividad de las células NK durante el embarazo normal. Por lo tanto, este estudio se centró en la caracterización de B7H6 soluble durante el desarrollo del embarazo normal. Se obtuvieron muestras de suero de mujeres embarazadas sanas que estaban experimentando su segundo embarazo (n = 36). Además, 17 de estas participantes embarazadas fueron estudiadas longitudinalmente por la presencia de B7H6 durante su segundo y tercer trimestres. Las mujeres no embarazadas sanas de la misma edad sirvieron como controles (n = 30). La presencia de 7H6 soluble se reveló mediante transferencia de Western. Se realizó una caracterización adicional utilizando un enfoque inmunoproteómico basado en 2DE-Western blotting combinado con MALDI-MS. Los resultados muestran que los sueros de todas las mujeres embarazadas se caracterizaron por la presencia de dos nuevas isoformas de B7H6, ambas con un MW más bajo que el reportado de 51 kDa. Estas isoformas eran una isoforma pesada (∼37 kDa) o ligera (∼30 kDa) y se excluían mutuamente. La N-glicosilación no explicó completamente los diferentes pesos moleculares exhibidos por las dos isoformas, como se demostró por la desglicosilación enzimática con PNGasa F. La confirmación de la identidad y la masa molecular de cada isoforma indica que B7H6, mientras que mantiene la C y N termini, es más probable que se libere durante el embarazo por un mecanismo distinto de la escisión proteolítica. Encontramos que ambas isoformas, pero principalmente la B7H6 más pesada, se liberaron a través de exosomas; y que la isoforma más ligera también se liberó de una manera libre de exosomas que no se observó en las muestras de isoformas pesadas. En conclusión, encontramos que el B7H6 soluble se expresa de forma constitutiva durante el embarazo y que, además, el B7H6 soluble está presente en dos nuevas isoformas, que se liberan mediante mecanismos exosómicos y exosomas.Immunobiology2018-10-04T20:11:59Z2018-10-04T20:11:59Z2018-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://dx.doi.org/10.1016/j.imbio.2017.10.0120171-2985http://dspace.uan.mx:8080/jspui/handle/123456789/1094https://www.sciencedirect.com/science/article/pii/S017129851730147Xreponame:Repositorio Institucional Aramara de la UANinstname:Universidad Autónoma de Nayaritinstacron:UANengPúblico en generalinfo:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/cc-by-nc-saoai:dspace.uan.mx:123456789/10942024-08-28T03:18:48Z
score 15.812429

Similar Items