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Modulation of Tetraspanin 32 (TSPAN32) Expression in T Cell-Mediated Immune Responses and in Multiple Sclerosis

Tetraspanins are a conserved family of proteins involved in a number of biological processes including, cell–cell interactions, fertility, cancer metastasis and immune responses. It has previously been shown that TSPAN32 knockout mice have normal hemopoiesis and B-cell responses, but hyperproliferat...

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Autores principales: Lombardo, Salvo Danilo, Mazzon, Emanuela, Basile, Maria Sofia, Campo, Giorgia, Corsico, Federica, Presti, Mario, Bramanti, Placido, Mangano, Katia, Petralia, Maria Cristina, Nicoletti, Ferdinando, Fagone, Paolo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770290/
https://www.ncbi.nlm.nih.gov/pubmed/31487788
http://dx.doi.org/10.3390/ijms20184323
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author Lombardo, Salvo Danilo
Mazzon, Emanuela
Basile, Maria Sofia
Campo, Giorgia
Corsico, Federica
Presti, Mario
Bramanti, Placido
Mangano, Katia
Petralia, Maria Cristina
Nicoletti, Ferdinando
Fagone, Paolo
author_facet Lombardo, Salvo Danilo
Mazzon, Emanuela
Basile, Maria Sofia
Campo, Giorgia
Corsico, Federica
Presti, Mario
Bramanti, Placido
Mangano, Katia
Petralia, Maria Cristina
Nicoletti, Ferdinando
Fagone, Paolo
author_sort Lombardo, Salvo Danilo
collection PubMed
description Tetraspanins are a conserved family of proteins involved in a number of biological processes including, cell–cell interactions, fertility, cancer metastasis and immune responses. It has previously been shown that TSPAN32 knockout mice have normal hemopoiesis and B-cell responses, but hyperproliferative T cells. Here, we show that TSPAN32 is expressed at higher levels in the lymphoid lineage as compared to myeloid cells. In vitro activation of T helper cells via anti-CD3/CD28 is associated with a significant downregulation of TSPAN32. Interestingly, engagement of CD3 is sufficient to modulate TSPAN32 expression, and its effect is potentiated by costimulation with anti-CD28, but not anti-CTLA4, -ICOS nor -PD1. Accordingly, we measured the transcriptomic levels of TSPAN32 in polarized T cells under Th1 and Th2 conditions and TSPAN32 resulted significantly reduced as compared with unstimulated cells. On the other hand, in Treg cells, TSPAN32 underwent minor changes upon activation. The in vitro data were finally translated into the context of multiple sclerosis (MS). Encephalitogenic T cells from Myelin Oligodendrocyte Glycoprotein (MOG)-Induced Experimental Autoimmune Encephalomyelitis (EAE) mice showed significantly lower levels of TSPAN32 and increased levels of CD9, CD53, CD82 and CD151. Similarly, in vitro-activated circulating CD4 T cells from MS patients showed lower levels of TSPAN32 as compared with cells from healthy donors. Overall, these data suggest an immunoregulatory role for TSPAN32 in T helper immune response and may represent a target of future immunoregulatory therapies for T cell-mediated autoimmune diseases.
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spelling pubmed-67702902019-10-30 Modulation of Tetraspanin 32 (TSPAN32) Expression in T Cell-Mediated Immune Responses and in Multiple Sclerosis Lombardo, Salvo Danilo Mazzon, Emanuela Basile, Maria Sofia Campo, Giorgia Corsico, Federica Presti, Mario Bramanti, Placido Mangano, Katia Petralia, Maria Cristina Nicoletti, Ferdinando Fagone, Paolo Int J Mol Sci Article Tetraspanins are a conserved family of proteins involved in a number of biological processes including, cell–cell interactions, fertility, cancer metastasis and immune responses. It has previously been shown that TSPAN32 knockout mice have normal hemopoiesis and B-cell responses, but hyperproliferative T cells. Here, we show that TSPAN32 is expressed at higher levels in the lymphoid lineage as compared to myeloid cells. In vitro activation of T helper cells via anti-CD3/CD28 is associated with a significant downregulation of TSPAN32. Interestingly, engagement of CD3 is sufficient to modulate TSPAN32 expression, and its effect is potentiated by costimulation with anti-CD28, but not anti-CTLA4, -ICOS nor -PD1. Accordingly, we measured the transcriptomic levels of TSPAN32 in polarized T cells under Th1 and Th2 conditions and TSPAN32 resulted significantly reduced as compared with unstimulated cells. On the other hand, in Treg cells, TSPAN32 underwent minor changes upon activation. The in vitro data were finally translated into the context of multiple sclerosis (MS). Encephalitogenic T cells from Myelin Oligodendrocyte Glycoprotein (MOG)-Induced Experimental Autoimmune Encephalomyelitis (EAE) mice showed significantly lower levels of TSPAN32 and increased levels of CD9, CD53, CD82 and CD151. Similarly, in vitro-activated circulating CD4 T cells from MS patients showed lower levels of TSPAN32 as compared with cells from healthy donors. Overall, these data suggest an immunoregulatory role for TSPAN32 in T helper immune response and may represent a target of future immunoregulatory therapies for T cell-mediated autoimmune diseases. MDPI 2019-09-04 /pmc/articles/PMC6770290/ /pubmed/31487788 http://dx.doi.org/10.3390/ijms20184323 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lombardo, Salvo Danilo
Mazzon, Emanuela
Basile, Maria Sofia
Campo, Giorgia
Corsico, Federica
Presti, Mario
Bramanti, Placido
Mangano, Katia
Petralia, Maria Cristina
Nicoletti, Ferdinando
Fagone, Paolo
Modulation of Tetraspanin 32 (TSPAN32) Expression in T Cell-Mediated Immune Responses and in Multiple Sclerosis
title Modulation of Tetraspanin 32 (TSPAN32) Expression in T Cell-Mediated Immune Responses and in Multiple Sclerosis
title_full Modulation of Tetraspanin 32 (TSPAN32) Expression in T Cell-Mediated Immune Responses and in Multiple Sclerosis
title_fullStr Modulation of Tetraspanin 32 (TSPAN32) Expression in T Cell-Mediated Immune Responses and in Multiple Sclerosis
title_full_unstemmed Modulation of Tetraspanin 32 (TSPAN32) Expression in T Cell-Mediated Immune Responses and in Multiple Sclerosis
title_short Modulation of Tetraspanin 32 (TSPAN32) Expression in T Cell-Mediated Immune Responses and in Multiple Sclerosis
title_sort modulation of tetraspanin 32 (tspan32) expression in t cell-mediated immune responses and in multiple sclerosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770290/
https://www.ncbi.nlm.nih.gov/pubmed/31487788
http://dx.doi.org/10.3390/ijms20184323
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