All-trans retinoic acid (ATRA) induces miR-23a expression, decreases CTSC expression and granzyme B activity leading to impaired NK cell cytotoxicity

Diego Sanchez-Martínez; Ewelina Krzywinska; Moeez G. Rathore; Anne Saumet; Amelie Cornillon; Nuria Lopez-Royuela; Luis Martínez-Lostao; Ariel Ramirez-Labrada; Zhao Yang Lu; Jean François Rossi; Dietmar Fernández-Orth; Sergio Escorza; Alberto Anel; Charles Henri Lecellier; Julian Pardo; Martin Villalba

doi:10.1016/j.biocel.2014.01.003

All-trans retinoic acid (ATRA) induces miR-23a expression, decreases CTSC expression and granzyme B activity leading to impaired NK cell cytotoxicity

Diego Sanchez-Martínez, Ewelina Krzywinska, Moeez G. Rathore, Anne Saumet, Amelie Cornillon, Nuria Lopez-Royuela, Luis Martínez-Lostao, Ariel Ramirez-Labrada, Zhao Yang Lu, Jean François Rossi, Dietmar Fernández-Orth, Sergio Escorza, Alberto Anel, Charles Henri Lecellier, Julian Pardo, Martin Villalba

Research output: Contribution to journal › Article › peer-review

35 Scopus citations

Abstract

NK cell is an innate immune system lymphocyte lineage with natural cytotoxicity. Its optimal use in the clinic requires in vitro expansion and activation. Cytokines and encounter with target cells activate NK cells and induce proliferation, and this could depend on the presence of other immune cells. Here we activated PBMCs during 5 days with IL-2, with IL-2 plus the tumor cell line K562 and with the lymphoblastoid cell line R69 and perform integrated analyses of microRNA and mRNA expression profiles of purified NK cells. The samples cluster depending on the stimuli and not on the donor, indicating that the pattern of NK cell stimulation is acutely well conserved between individuals. Regulation of mRNA expression is tighter than that of miRNA expression. All stimuli induce a common preserved genetic remodeling. In addition, encounter with target cells mainly activates pathways related to metabolism. Different target cells induce different NK cell remodeling which affects cytokine response and cytotoxicity, supporting the notion that encounter with different target cells significantly changing the activation pattern. We validate our analysis by showing that activation down regulates miR-23a, which is a negative regulator of cathepsin C (CTSC) mRNA, a gene up regulated by all stimuli. The peptidase CTSC activates the granzymes, the main effector proteases involved in NK cell cytotoxicity. All-trans retinoic acid (ATRA), which induces miR-23a expression, decreases CTSC expression and granzyme B activity leading to impaired NK cell cytotoxicity in an in vivo mouse model.

Original language	English (US)
Pages (from-to)	42-52
Number of pages	11
Journal	International Journal of Biochemistry and Cell Biology
Volume	49
Issue number	1
DOIs	https://doi.org/10.1016/j.biocel.2014.01.003
State	Published - Apr 2014
Externally published	Yes

Bibliographical note

Funding Information:
This work was supported by the program “Chercheur d’avenir” from the Region Languedoc-Rousillon (MV), a scientific program from the “Communauté de Travail des Pyrénées” (CTPP10/09 to MV, SE and AA), the CliNK project (SOE2/P1/E341) from Sudoe/EU (AA, J-FR and MV), the Association pour la Recherche contre le Cancer (MV), the Fondation pour la Recherche Medicale (MV), a grant FEDER Objectif competitivite (MV), l’association CIEL, l’association L’Un pour l’Autre et la fédération Ensangble (MV), Fondo Social Europeo (FSE), grants SAF2010-15341 (AA) and SAF2011-25390 (JP) Ministerio de Economía y Competitividad , Spain and fellowships from Gobierno de Aragon (DS) the ARC (MGR and EK) and Higher Education Commission, Pakistan (MGR) and La Ligue contre le Cancer (NL-R).

Keywords

Cathepsin C
NK cells
Transcriptomics
miR-23a
miRNA

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access

10.1016/j.biocel.2014.01.003

OpenUrl availability

Full text

Cite this

Sanchez-Martínez, D., Krzywinska, E., Rathore, M. G., Saumet, A., Cornillon, A., Lopez-Royuela, N., Martínez-Lostao, L., Ramirez-Labrada, A., Lu, Z. Y., Rossi, J. F., Fernández-Orth, D., Escorza, S., Anel, A., Lecellier, C. H., Pardo, J., & Villalba, M. (2014). All-trans retinoic acid (ATRA) induces miR-23a expression, decreases CTSC expression and granzyme B activity leading to impaired NK cell cytotoxicity. International Journal of Biochemistry and Cell Biology, 49(1), 42-52. https://doi.org/10.1016/j.biocel.2014.01.003

All-trans retinoic acid (ATRA) induces miR-23a expression, decreases CTSC expression and granzyme B activity leading to impaired NK cell cytotoxicity. / Sanchez-Martínez, Diego; Krzywinska, Ewelina; Rathore, Moeez G. et al.
In: International Journal of Biochemistry and Cell Biology, Vol. 49, No. 1, 04.2014, p. 42-52.

Research output: Contribution to journal › Article › peer-review

Sanchez-Martínez, D, Krzywinska, E, Rathore, MG, Saumet, A, Cornillon, A, Lopez-Royuela, N, Martínez-Lostao, L, Ramirez-Labrada, A, Lu, ZY, Rossi, JF, Fernández-Orth, D, Escorza, S, Anel, A, Lecellier, CH, Pardo, J & Villalba, M 2014, 'All-trans retinoic acid (ATRA) induces miR-23a expression, decreases CTSC expression and granzyme B activity leading to impaired NK cell cytotoxicity', International Journal of Biochemistry and Cell Biology, vol. 49, no. 1, pp. 42-52. https://doi.org/10.1016/j.biocel.2014.01.003

@article{1964f4333496401480c48e9955b239d9,

title = "All-trans retinoic acid (ATRA) induces miR-23a expression, decreases CTSC expression and granzyme B activity leading to impaired NK cell cytotoxicity",

abstract = "NK cell is an innate immune system lymphocyte lineage with natural cytotoxicity. Its optimal use in the clinic requires in vitro expansion and activation. Cytokines and encounter with target cells activate NK cells and induce proliferation, and this could depend on the presence of other immune cells. Here we activated PBMCs during 5 days with IL-2, with IL-2 plus the tumor cell line K562 and with the lymphoblastoid cell line R69 and perform integrated analyses of microRNA and mRNA expression profiles of purified NK cells. The samples cluster depending on the stimuli and not on the donor, indicating that the pattern of NK cell stimulation is acutely well conserved between individuals. Regulation of mRNA expression is tighter than that of miRNA expression. All stimuli induce a common preserved genetic remodeling. In addition, encounter with target cells mainly activates pathways related to metabolism. Different target cells induce different NK cell remodeling which affects cytokine response and cytotoxicity, supporting the notion that encounter with different target cells significantly changing the activation pattern. We validate our analysis by showing that activation down regulates miR-23a, which is a negative regulator of cathepsin C (CTSC) mRNA, a gene up regulated by all stimuli. The peptidase CTSC activates the granzymes, the main effector proteases involved in NK cell cytotoxicity. All-trans retinoic acid (ATRA), which induces miR-23a expression, decreases CTSC expression and granzyme B activity leading to impaired NK cell cytotoxicity in an in vivo mouse model.",

keywords = "Cathepsin C, NK cells, Transcriptomics, miR-23a, miRNA",

author = "Diego Sanchez-Mart{\'i}nez and Ewelina Krzywinska and Rathore, {Moeez G.} and Anne Saumet and Amelie Cornillon and Nuria Lopez-Royuela and Luis Mart{\'i}nez-Lostao and Ariel Ramirez-Labrada and Lu, {Zhao Yang} and Rossi, {Jean Fran{\c c}ois} and Dietmar Fern{\'a}ndez-Orth and Sergio Escorza and Alberto Anel and Lecellier, {Charles Henri} and Julian Pardo and Martin Villalba",

note = "Funding Information: This work was supported by the program “Chercheur d{\textquoteright}avenir” from the Region Languedoc-Rousillon (MV), a scientific program from the “Communaut{\'e} de Travail des Pyr{\'e}n{\'e}es” (CTPP10/09 to MV, SE and AA), the CliNK project (SOE2/P1/E341) from Sudoe/EU (AA, J-FR and MV), the Association pour la Recherche contre le Cancer (MV), the Fondation pour la Recherche Medicale (MV), a grant FEDER Objectif competitivite (MV), l{\textquoteright}association CIEL, l{\textquoteright}association L{\textquoteright}Un pour l{\textquoteright}Autre et la f{\'e}d{\'e}ration Ensangble (MV), Fondo Social Europeo (FSE), grants SAF2010-15341 (AA) and SAF2011-25390 (JP) Ministerio de Econom{\'i}a y Competitividad , Spain and fellowships from Gobierno de Aragon (DS) the ARC (MGR and EK) and Higher Education Commission, Pakistan (MGR) and La Ligue contre le Cancer (NL-R). ",

year = "2014",

month = apr,

doi = "10.1016/j.biocel.2014.01.003",

language = "English (US)",

volume = "49",

pages = "42--52",

journal = "International Journal of Biochemistry and Cell Biology",

issn = "1357-2725",

publisher = "Elsevier Limited",

number = "1",

}

TY - JOUR

T1 - All-trans retinoic acid (ATRA) induces miR-23a expression, decreases CTSC expression and granzyme B activity leading to impaired NK cell cytotoxicity

AU - Sanchez-Martínez, Diego

AU - Krzywinska, Ewelina

AU - Rathore, Moeez G.

AU - Saumet, Anne

AU - Cornillon, Amelie

AU - Lopez-Royuela, Nuria

AU - Martínez-Lostao, Luis

AU - Ramirez-Labrada, Ariel

AU - Lu, Zhao Yang

AU - Rossi, Jean François

AU - Fernández-Orth, Dietmar

AU - Escorza, Sergio

AU - Anel, Alberto

AU - Lecellier, Charles Henri

AU - Pardo, Julian

AU - Villalba, Martin

N1 - Funding Information: This work was supported by the program “Chercheur d’avenir” from the Region Languedoc-Rousillon (MV), a scientific program from the “Communauté de Travail des Pyrénées” (CTPP10/09 to MV, SE and AA), the CliNK project (SOE2/P1/E341) from Sudoe/EU (AA, J-FR and MV), the Association pour la Recherche contre le Cancer (MV), the Fondation pour la Recherche Medicale (MV), a grant FEDER Objectif competitivite (MV), l’association CIEL, l’association L’Un pour l’Autre et la fédération Ensangble (MV), Fondo Social Europeo (FSE), grants SAF2010-15341 (AA) and SAF2011-25390 (JP) Ministerio de Economía y Competitividad , Spain and fellowships from Gobierno de Aragon (DS) the ARC (MGR and EK) and Higher Education Commission, Pakistan (MGR) and La Ligue contre le Cancer (NL-R).

PY - 2014/4

Y1 - 2014/4

N2 - NK cell is an innate immune system lymphocyte lineage with natural cytotoxicity. Its optimal use in the clinic requires in vitro expansion and activation. Cytokines and encounter with target cells activate NK cells and induce proliferation, and this could depend on the presence of other immune cells. Here we activated PBMCs during 5 days with IL-2, with IL-2 plus the tumor cell line K562 and with the lymphoblastoid cell line R69 and perform integrated analyses of microRNA and mRNA expression profiles of purified NK cells. The samples cluster depending on the stimuli and not on the donor, indicating that the pattern of NK cell stimulation is acutely well conserved between individuals. Regulation of mRNA expression is tighter than that of miRNA expression. All stimuli induce a common preserved genetic remodeling. In addition, encounter with target cells mainly activates pathways related to metabolism. Different target cells induce different NK cell remodeling which affects cytokine response and cytotoxicity, supporting the notion that encounter with different target cells significantly changing the activation pattern. We validate our analysis by showing that activation down regulates miR-23a, which is a negative regulator of cathepsin C (CTSC) mRNA, a gene up regulated by all stimuli. The peptidase CTSC activates the granzymes, the main effector proteases involved in NK cell cytotoxicity. All-trans retinoic acid (ATRA), which induces miR-23a expression, decreases CTSC expression and granzyme B activity leading to impaired NK cell cytotoxicity in an in vivo mouse model.

AB - NK cell is an innate immune system lymphocyte lineage with natural cytotoxicity. Its optimal use in the clinic requires in vitro expansion and activation. Cytokines and encounter with target cells activate NK cells and induce proliferation, and this could depend on the presence of other immune cells. Here we activated PBMCs during 5 days with IL-2, with IL-2 plus the tumor cell line K562 and with the lymphoblastoid cell line R69 and perform integrated analyses of microRNA and mRNA expression profiles of purified NK cells. The samples cluster depending on the stimuli and not on the donor, indicating that the pattern of NK cell stimulation is acutely well conserved between individuals. Regulation of mRNA expression is tighter than that of miRNA expression. All stimuli induce a common preserved genetic remodeling. In addition, encounter with target cells mainly activates pathways related to metabolism. Different target cells induce different NK cell remodeling which affects cytokine response and cytotoxicity, supporting the notion that encounter with different target cells significantly changing the activation pattern. We validate our analysis by showing that activation down regulates miR-23a, which is a negative regulator of cathepsin C (CTSC) mRNA, a gene up regulated by all stimuli. The peptidase CTSC activates the granzymes, the main effector proteases involved in NK cell cytotoxicity. All-trans retinoic acid (ATRA), which induces miR-23a expression, decreases CTSC expression and granzyme B activity leading to impaired NK cell cytotoxicity in an in vivo mouse model.

KW - Cathepsin C

KW - NK cells

KW - Transcriptomics

KW - miR-23a

KW - miRNA

UR - http://www.scopus.com/inward/record.url?scp=84893476736&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84893476736&partnerID=8YFLogxK

U2 - 10.1016/j.biocel.2014.01.003

DO - 10.1016/j.biocel.2014.01.003

M3 - Article

C2 - 24440757

AN - SCOPUS:84893476736

SN - 1357-2725

VL - 49

SP - 42

EP - 52

JO - International Journal of Biochemistry and Cell Biology

JF - International Journal of Biochemistry and Cell Biology

IS - 1

ER -

All-trans retinoic acid (ATRA) induces miR-23a expression, decreases CTSC expression and granzyme B activity leading to impaired NK cell cytotoxicity

Abstract

Bibliographical note

Keywords

UN SDGs

Access

OpenUrl availability

Other files and links

Fingerprint

Cite this