SIRPγ-CD47 Interaction Positively Regulates the Activation of Human T Cells in Situation of Chronic Stimulation

A numerous number of positive and negative signals via various molecules modulate T-cell activation. Within the various transmembrane proteins, SIRPγ is of interest since it is not expressed in rodents. SIRPγ interaction with CD47 is reevaluated in this study. Indeed, we show that the anti-SIRPγ mAb...

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Autores principales:	Safa Dehmani, Véronique Nerrière-Daguin, Mélanie Néel, Nathan Elain-Duret, Jean-Marie Heslan, Lyssia Belarif, Caroline Mary, Virginie Thepenier, Kevin Biteau, Nicolas Poirier, Gilles Blancho, Fabienne Haspot
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	graft-versus-host disease SIRPA chronic stimulation T cell CD47 SIRPG Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/e739c9f323054f98b7a63928ad4cb2fa
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spelling	oai:doaj.org-article:e739c9f323054f98b7a63928ad4cb2fa2021-12-01T21:21:04ZSIRPγ-CD47 Interaction Positively Regulates the Activation of Human T Cells in Situation of Chronic Stimulation1664-322410.3389/fimmu.2021.732530https://doaj.org/article/e739c9f323054f98b7a63928ad4cb2fa2021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.732530/fullhttps://doaj.org/toc/1664-3224A numerous number of positive and negative signals via various molecules modulate T-cell activation. Within the various transmembrane proteins, SIRPγ is of interest since it is not expressed in rodents. SIRPγ interaction with CD47 is reevaluated in this study. Indeed, we show that the anti-SIRPγ mAb clone LSB2.20 previously used by others has not been appropriately characterized. We reveal that the anti-SIRPα clone KWAR23 is a Pan anti-SIRP mAb which efficiently blocks SIRPα and SIRPγ interactions with CD47. We show that SIRPγ expression on T cells varies with their differentiation and while being expressed on Tregs, is not implicated in their suppressive functions. SIRPγ spatial reorganization at the immune synapse is independent of its interaction with CD47. In vitro SIRPα-γ/CD47 blockade with KWAR23 impairs IFN-γ secretion by chronically activated T cells. In vivo in a xeno-GvHD model in NSG mice, the SIRPγ/CD47 blockade with the KWAR23 significantly delays the onset of the xeno-GvHD and deeply impairs human chimerism. In conclusion, we have shown that T-cell interaction with CD47 is of importance notably in chronic stimulation.Safa DehmaniSafa DehmaniVéronique Nerrière-DaguinMélanie NéelNathan Elain-DuretJean-Marie HeslanLyssia BelarifCaroline MaryVirginie ThepenierKevin BiteauNicolas PoirierGilles BlanchoFabienne HaspotFrontiers Media S.A.articlegraft-versus-host diseaseSIRPAchronic stimulationT cellCD47SIRPGImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	graft-versus-host disease SIRPA chronic stimulation T cell CD47 SIRPG Immunologic diseases. Allergy RC581-607
spellingShingle	graft-versus-host disease SIRPA chronic stimulation T cell CD47 SIRPG Immunologic diseases. Allergy RC581-607 Safa Dehmani Safa Dehmani Véronique Nerrière-Daguin Mélanie Néel Nathan Elain-Duret Jean-Marie Heslan Lyssia Belarif Caroline Mary Virginie Thepenier Kevin Biteau Nicolas Poirier Gilles Blancho Fabienne Haspot SIRPγ-CD47 Interaction Positively Regulates the Activation of Human T Cells in Situation of Chronic Stimulation
description	A numerous number of positive and negative signals via various molecules modulate T-cell activation. Within the various transmembrane proteins, SIRPγ is of interest since it is not expressed in rodents. SIRPγ interaction with CD47 is reevaluated in this study. Indeed, we show that the anti-SIRPγ mAb clone LSB2.20 previously used by others has not been appropriately characterized. We reveal that the anti-SIRPα clone KWAR23 is a Pan anti-SIRP mAb which efficiently blocks SIRPα and SIRPγ interactions with CD47. We show that SIRPγ expression on T cells varies with their differentiation and while being expressed on Tregs, is not implicated in their suppressive functions. SIRPγ spatial reorganization at the immune synapse is independent of its interaction with CD47. In vitro SIRPα-γ/CD47 blockade with KWAR23 impairs IFN-γ secretion by chronically activated T cells. In vivo in a xeno-GvHD model in NSG mice, the SIRPγ/CD47 blockade with the KWAR23 significantly delays the onset of the xeno-GvHD and deeply impairs human chimerism. In conclusion, we have shown that T-cell interaction with CD47 is of importance notably in chronic stimulation.
format	article
author	Safa Dehmani Safa Dehmani Véronique Nerrière-Daguin Mélanie Néel Nathan Elain-Duret Jean-Marie Heslan Lyssia Belarif Caroline Mary Virginie Thepenier Kevin Biteau Nicolas Poirier Gilles Blancho Fabienne Haspot
author_facet	Safa Dehmani Safa Dehmani Véronique Nerrière-Daguin Mélanie Néel Nathan Elain-Duret Jean-Marie Heslan Lyssia Belarif Caroline Mary Virginie Thepenier Kevin Biteau Nicolas Poirier Gilles Blancho Fabienne Haspot
author_sort	Safa Dehmani
title	SIRPγ-CD47 Interaction Positively Regulates the Activation of Human T Cells in Situation of Chronic Stimulation
title_short	SIRPγ-CD47 Interaction Positively Regulates the Activation of Human T Cells in Situation of Chronic Stimulation
title_full	SIRPγ-CD47 Interaction Positively Regulates the Activation of Human T Cells in Situation of Chronic Stimulation
title_fullStr	SIRPγ-CD47 Interaction Positively Regulates the Activation of Human T Cells in Situation of Chronic Stimulation
title_full_unstemmed	SIRPγ-CD47 Interaction Positively Regulates the Activation of Human T Cells in Situation of Chronic Stimulation
title_sort	sirpγ-cd47 interaction positively regulates the activation of human t cells in situation of chronic stimulation
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/e739c9f323054f98b7a63928ad4cb2fa
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SIRPγ-CD47 Interaction Positively Regulates the Activation of Human T Cells in Situation of Chronic Stimulation

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