CD38 Correlates with an Immunosuppressive Treg Phenotype in Lupus-Prone Mice

CD38 is a transmembrane glycoprotein expressed by T-cells. It has been reported that patients with systemic lupus erythematosus (SLE) showed increased CD38<sup>+</sup>CD25<sup>+</sup> T-cells correlating with immune activation and clinical signs. Contrariwise, CD38 deficiency...

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Autores principales:	Jocelyn C. Pérez-Lara, Enrique Espinosa, Leopoldo Santos-Argumedo, Héctor Romero-Ramírez, Gabriela López-Herrera, Fabio García-García, Claudia Sandoval-Montes, Vianney Ortiz-Navarrete, Mónica Flores-Muñoz, Juan C. Rodríguez-Alba
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	CD38 regulatory T-cells systemic lupus erythematosus immunosuppressive lupus-prone mice IFN-γ Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/258ef1a4062941bc9cf0af1f6c772ade
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spelling	oai:doaj.org-article:258ef1a4062941bc9cf0af1f6c772ade2021-11-11T17:23:49ZCD38 Correlates with an Immunosuppressive Treg Phenotype in Lupus-Prone Mice10.3390/ijms2221119771422-00671661-6596https://doaj.org/article/258ef1a4062941bc9cf0af1f6c772ade2021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11977https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067CD38 is a transmembrane glycoprotein expressed by T-cells. It has been reported that patients with systemic lupus erythematosus (SLE) showed increased CD38<sup>+</sup>CD25<sup>+</sup> T-cells correlating with immune activation and clinical signs. Contrariwise, CD38 deficiency in murine models has shown enhanced autoimmunity development. Recent studies have suggested that CD38<sup>+</sup> regulatory T-cells are more suppressive than CD38<sup>−</sup> regulatory T-cells. Thus, we have suggested that CD38 overexpression in SLE patients could play a role in regulating immune activation cells instead of enhancing it. This study found a correlation between CD38 with FoxP3 expression and immunosuppressive molecules (CD69, IL-10, CTLA-4, and PD-1) in T-cells from lupus-prone mice (B6.MRL-Fas<sup>lpr</sup>/J). Additionally, B6.MRL-Fas<sup>lpr</sup>/J mice showed a decreased proportion of CD38<sup>+</sup> Treg cells regarding wild-type mice (WT). Furthermore, Regulatory T-Cells (Treg cells) from <i>CD38-/-</i> mice showed impairment in expressing immunosuppressive molecules and proliferation after stimulation through the T-cell receptor (TCR). Finally, we demonstrated an increased ratio of IFN-γ/IL-10 secretion in <i>CD38-/-</i> splenocytes stimulated with anti-CD3 compared with the WT. Altogether, our data suggest that CD38 represents an element in maintaining activated and proliferative Treg cells. Consequently, CD38 could have a crucial role in immune tolerance, preventing SLE development through Treg cells.Jocelyn C. Pérez-LaraEnrique EspinosaLeopoldo Santos-ArgumedoHéctor Romero-RamírezGabriela López-HerreraFabio García-GarcíaClaudia Sandoval-MontesVianney Ortiz-NavarreteMónica Flores-MuñozJuan C. Rodríguez-AlbaMDPI AGarticleCD38regulatory T-cellssystemic lupus erythematosusimmunosuppressivelupus-prone miceIFN-γBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11977, p 11977 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	CD38 regulatory T-cells systemic lupus erythematosus immunosuppressive lupus-prone mice IFN-γ Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	CD38 regulatory T-cells systemic lupus erythematosus immunosuppressive lupus-prone mice IFN-γ Biology (General) QH301-705.5 Chemistry QD1-999 Jocelyn C. Pérez-Lara Enrique Espinosa Leopoldo Santos-Argumedo Héctor Romero-Ramírez Gabriela López-Herrera Fabio García-García Claudia Sandoval-Montes Vianney Ortiz-Navarrete Mónica Flores-Muñoz Juan C. Rodríguez-Alba CD38 Correlates with an Immunosuppressive Treg Phenotype in Lupus-Prone Mice
description	CD38 is a transmembrane glycoprotein expressed by T-cells. It has been reported that patients with systemic lupus erythematosus (SLE) showed increased CD38<sup>+</sup>CD25<sup>+</sup> T-cells correlating with immune activation and clinical signs. Contrariwise, CD38 deficiency in murine models has shown enhanced autoimmunity development. Recent studies have suggested that CD38<sup>+</sup> regulatory T-cells are more suppressive than CD38<sup>−</sup> regulatory T-cells. Thus, we have suggested that CD38 overexpression in SLE patients could play a role in regulating immune activation cells instead of enhancing it. This study found a correlation between CD38 with FoxP3 expression and immunosuppressive molecules (CD69, IL-10, CTLA-4, and PD-1) in T-cells from lupus-prone mice (B6.MRL-Fas<sup>lpr</sup>/J). Additionally, B6.MRL-Fas<sup>lpr</sup>/J mice showed a decreased proportion of CD38<sup>+</sup> Treg cells regarding wild-type mice (WT). Furthermore, Regulatory T-Cells (Treg cells) from <i>CD38-/-</i> mice showed impairment in expressing immunosuppressive molecules and proliferation after stimulation through the T-cell receptor (TCR). Finally, we demonstrated an increased ratio of IFN-γ/IL-10 secretion in <i>CD38-/-</i> splenocytes stimulated with anti-CD3 compared with the WT. Altogether, our data suggest that CD38 represents an element in maintaining activated and proliferative Treg cells. Consequently, CD38 could have a crucial role in immune tolerance, preventing SLE development through Treg cells.
format	article
author	Jocelyn C. Pérez-Lara Enrique Espinosa Leopoldo Santos-Argumedo Héctor Romero-Ramírez Gabriela López-Herrera Fabio García-García Claudia Sandoval-Montes Vianney Ortiz-Navarrete Mónica Flores-Muñoz Juan C. Rodríguez-Alba
author_facet	Jocelyn C. Pérez-Lara Enrique Espinosa Leopoldo Santos-Argumedo Héctor Romero-Ramírez Gabriela López-Herrera Fabio García-García Claudia Sandoval-Montes Vianney Ortiz-Navarrete Mónica Flores-Muñoz Juan C. Rodríguez-Alba
author_sort	Jocelyn C. Pérez-Lara
title	CD38 Correlates with an Immunosuppressive Treg Phenotype in Lupus-Prone Mice
title_short	CD38 Correlates with an Immunosuppressive Treg Phenotype in Lupus-Prone Mice
title_full	CD38 Correlates with an Immunosuppressive Treg Phenotype in Lupus-Prone Mice
title_fullStr	CD38 Correlates with an Immunosuppressive Treg Phenotype in Lupus-Prone Mice
title_full_unstemmed	CD38 Correlates with an Immunosuppressive Treg Phenotype in Lupus-Prone Mice
title_sort	cd38 correlates with an immunosuppressive treg phenotype in lupus-prone mice
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/258ef1a4062941bc9cf0af1f6c772ade
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CD38 Correlates with an Immunosuppressive Treg Phenotype in Lupus-Prone Mice

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