The spliceosomal phosphopeptide P140 controls the lupus disease by interacting with the HSC70 protein and via a mechanism mediated by gammadelta T cells.

The phosphopeptide P140 issued from the spliceosomal U1-70K snRNP protein is recognized by lupus CD4(+) T cells, transiently abolishes T cell reactivity to other spliceosomal peptides in P140-treated MRL/lpr mice, and ameliorates their clinical features. P140 modulates lupus patients' T cell re...

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Autores principales:	Nicolas Page, Nicolas Schall, Jean-Marc Strub, Marc Quinternet, Olivier Chaloin, Marion Décossas, Manh Thong Cung, Alain Van Dorsselaer, Jean-Paul Briand, Sylviane Muller
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ad65138e2cc64a04869b8371bfe0ef37
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spelling	oai:doaj.org-article:ad65138e2cc64a04869b8371bfe0ef372021-11-25T06:23:04ZThe spliceosomal phosphopeptide P140 controls the lupus disease by interacting with the HSC70 protein and via a mechanism mediated by gammadelta T cells.1932-620310.1371/journal.pone.0005273https://doaj.org/article/ad65138e2cc64a04869b8371bfe0ef372009-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19390596/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203The phosphopeptide P140 issued from the spliceosomal U1-70K snRNP protein is recognized by lupus CD4(+) T cells, transiently abolishes T cell reactivity to other spliceosomal peptides in P140-treated MRL/lpr mice, and ameliorates their clinical features. P140 modulates lupus patients' T cell response ex vivo and is currently included in phase IIb clinical trials. Its underlying mechanism of action remains elusive. Here we show that P140 peptide binds a unique cell-surface receptor, the constitutively-expressed chaperone HSC70 protein, known as a presenting-protein. P140 induces apoptosis of activated MRL/lpr CD4(+) T cells. In P140-treated mice, it increases peripheral blood lymphocyte apoptosis and decreases B cell, activated T cell, and CD4(-)CD8(-)B220(+) T cell counts via a specific mechanism strictly depending on gammadelta T cells. Expression of inflammation-linked genes is rapidly regulated in CD4(+) T cells. This work led us to identify a powerful pathway taken by a newly-designed therapeutic peptide to immunomodulate lupus autoimmunity.Nicolas PageNicolas SchallJean-Marc StrubMarc QuinternetOlivier ChaloinMarion DécossasManh Thong CungAlain Van DorsselaerJean-Paul BriandSylviane MullerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 4, Iss 4, p e5273 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nicolas Page Nicolas Schall Jean-Marc Strub Marc Quinternet Olivier Chaloin Marion Décossas Manh Thong Cung Alain Van Dorsselaer Jean-Paul Briand Sylviane Muller The spliceosomal phosphopeptide P140 controls the lupus disease by interacting with the HSC70 protein and via a mechanism mediated by gammadelta T cells.
description	The phosphopeptide P140 issued from the spliceosomal U1-70K snRNP protein is recognized by lupus CD4(+) T cells, transiently abolishes T cell reactivity to other spliceosomal peptides in P140-treated MRL/lpr mice, and ameliorates their clinical features. P140 modulates lupus patients' T cell response ex vivo and is currently included in phase IIb clinical trials. Its underlying mechanism of action remains elusive. Here we show that P140 peptide binds a unique cell-surface receptor, the constitutively-expressed chaperone HSC70 protein, known as a presenting-protein. P140 induces apoptosis of activated MRL/lpr CD4(+) T cells. In P140-treated mice, it increases peripheral blood lymphocyte apoptosis and decreases B cell, activated T cell, and CD4(-)CD8(-)B220(+) T cell counts via a specific mechanism strictly depending on gammadelta T cells. Expression of inflammation-linked genes is rapidly regulated in CD4(+) T cells. This work led us to identify a powerful pathway taken by a newly-designed therapeutic peptide to immunomodulate lupus autoimmunity.
format	article
author	Nicolas Page Nicolas Schall Jean-Marc Strub Marc Quinternet Olivier Chaloin Marion Décossas Manh Thong Cung Alain Van Dorsselaer Jean-Paul Briand Sylviane Muller
author_facet	Nicolas Page Nicolas Schall Jean-Marc Strub Marc Quinternet Olivier Chaloin Marion Décossas Manh Thong Cung Alain Van Dorsselaer Jean-Paul Briand Sylviane Muller
author_sort	Nicolas Page
title	The spliceosomal phosphopeptide P140 controls the lupus disease by interacting with the HSC70 protein and via a mechanism mediated by gammadelta T cells.
title_short	The spliceosomal phosphopeptide P140 controls the lupus disease by interacting with the HSC70 protein and via a mechanism mediated by gammadelta T cells.
title_full	The spliceosomal phosphopeptide P140 controls the lupus disease by interacting with the HSC70 protein and via a mechanism mediated by gammadelta T cells.
title_fullStr	The spliceosomal phosphopeptide P140 controls the lupus disease by interacting with the HSC70 protein and via a mechanism mediated by gammadelta T cells.
title_full_unstemmed	The spliceosomal phosphopeptide P140 controls the lupus disease by interacting with the HSC70 protein and via a mechanism mediated by gammadelta T cells.
title_sort	spliceosomal phosphopeptide p140 controls the lupus disease by interacting with the hsc70 protein and via a mechanism mediated by gammadelta t cells.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/ad65138e2cc64a04869b8371bfe0ef37
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The spliceosomal phosphopeptide P140 controls the lupus disease by interacting with the HSC70 protein and via a mechanism mediated by gammadelta T cells.

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