Enhanced inflammatory potential of CD4+ T-cells that lack proteasome immunosubunit expression, in a T-cell transfer-based colitis model.

Proteasomes play a fundamental role in intracellular protein degradation and therewith regulate a variety of cellular processes. Exposure of cells to (pro)inflammatory cytokines upregulates the expression of three inducible catalytic proteasome subunits, the immunosubunits, which incorporate into ne...

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Autores principales:	Orhan Rasid, Chantal Meulenbroeks, Andrea Gröne, Dietmar Zaiss, Alice Sijts
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6256ed97b95a40d49593c2a16a355e7b
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spelling	oai:doaj.org-article:6256ed97b95a40d49593c2a16a355e7b2021-11-18T08:22:50ZEnhanced inflammatory potential of CD4+ T-cells that lack proteasome immunosubunit expression, in a T-cell transfer-based colitis model.1932-620310.1371/journal.pone.0095378https://doaj.org/article/6256ed97b95a40d49593c2a16a355e7b2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24740379/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Proteasomes play a fundamental role in intracellular protein degradation and therewith regulate a variety of cellular processes. Exposure of cells to (pro)inflammatory cytokines upregulates the expression of three inducible catalytic proteasome subunits, the immunosubunits, which incorporate into newly assembled proteasome complexes and alter the catalytic activity of the cellular proteasome population. Single gene-deficient mice lacking one of the three immunosubunits are resistant to dextran sulfate sodium (DSS)-induced colitis development and, likewise, inhibition of one single immunosubunit protects mice against the development of DSS-induced colitis. The observed diminished disease susceptibility has been attributed to altered cytokine production and CD4+ T-cell differentiation in the absence of immunosubunits. To further test whether the catalytic activity conferred by immunosubunits plays an essential role in CD4+ T-cell function and to distinguish between the role of immunosubunits in effector T-cells versus inflamed tissue, we used a T-cell transfer-induced colitis model. Naïve wt or immunosubunit-deficient CD4+ T-cells were adoptively transferred into RAG1-/- and immunosubunit-deficient RAG1-/- mice and colitis development was determined six weeks later. While immunosubunit expression in recipient mice had no effect on colitis development, transferred immunosubunit-deficient T- cells were more potent in inducing colitis and produced more proinflammatory IL17 than wt T-cells. Taken together, our data show that modifications in proteasome-mediated proteolysis in T-cells, conferred by lack of immunosubunit incorporation, do not attenuate but enhance CD4+ T-cell-induced inflammation.Orhan RasidChantal MeulenbroeksAndrea GröneDietmar ZaissAlice SijtsPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 4, p e95378 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Orhan Rasid Chantal Meulenbroeks Andrea Gröne Dietmar Zaiss Alice Sijts Enhanced inflammatory potential of CD4+ T-cells that lack proteasome immunosubunit expression, in a T-cell transfer-based colitis model.
description	Proteasomes play a fundamental role in intracellular protein degradation and therewith regulate a variety of cellular processes. Exposure of cells to (pro)inflammatory cytokines upregulates the expression of three inducible catalytic proteasome subunits, the immunosubunits, which incorporate into newly assembled proteasome complexes and alter the catalytic activity of the cellular proteasome population. Single gene-deficient mice lacking one of the three immunosubunits are resistant to dextran sulfate sodium (DSS)-induced colitis development and, likewise, inhibition of one single immunosubunit protects mice against the development of DSS-induced colitis. The observed diminished disease susceptibility has been attributed to altered cytokine production and CD4+ T-cell differentiation in the absence of immunosubunits. To further test whether the catalytic activity conferred by immunosubunits plays an essential role in CD4+ T-cell function and to distinguish between the role of immunosubunits in effector T-cells versus inflamed tissue, we used a T-cell transfer-induced colitis model. Naïve wt or immunosubunit-deficient CD4+ T-cells were adoptively transferred into RAG1-/- and immunosubunit-deficient RAG1-/- mice and colitis development was determined six weeks later. While immunosubunit expression in recipient mice had no effect on colitis development, transferred immunosubunit-deficient T- cells were more potent in inducing colitis and produced more proinflammatory IL17 than wt T-cells. Taken together, our data show that modifications in proteasome-mediated proteolysis in T-cells, conferred by lack of immunosubunit incorporation, do not attenuate but enhance CD4+ T-cell-induced inflammation.
format	article
author	Orhan Rasid Chantal Meulenbroeks Andrea Gröne Dietmar Zaiss Alice Sijts
author_facet	Orhan Rasid Chantal Meulenbroeks Andrea Gröne Dietmar Zaiss Alice Sijts
author_sort	Orhan Rasid
title	Enhanced inflammatory potential of CD4+ T-cells that lack proteasome immunosubunit expression, in a T-cell transfer-based colitis model.
title_short	Enhanced inflammatory potential of CD4+ T-cells that lack proteasome immunosubunit expression, in a T-cell transfer-based colitis model.
title_full	Enhanced inflammatory potential of CD4+ T-cells that lack proteasome immunosubunit expression, in a T-cell transfer-based colitis model.
title_fullStr	Enhanced inflammatory potential of CD4+ T-cells that lack proteasome immunosubunit expression, in a T-cell transfer-based colitis model.
title_full_unstemmed	Enhanced inflammatory potential of CD4+ T-cells that lack proteasome immunosubunit expression, in a T-cell transfer-based colitis model.
title_sort	enhanced inflammatory potential of cd4+ t-cells that lack proteasome immunosubunit expression, in a t-cell transfer-based colitis model.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/6256ed97b95a40d49593c2a16a355e7b
work_keys_str_mv	AT orhanrasid enhancedinflammatorypotentialofcd4tcellsthatlackproteasomeimmunosubunitexpressioninatcelltransferbasedcolitismodel AT chantalmeulenbroeks enhancedinflammatorypotentialofcd4tcellsthatlackproteasomeimmunosubunitexpressioninatcelltransferbasedcolitismodel AT andreagrone enhancedinflammatorypotentialofcd4tcellsthatlackproteasomeimmunosubunitexpressioninatcelltransferbasedcolitismodel AT dietmarzaiss enhancedinflammatorypotentialofcd4tcellsthatlackproteasomeimmunosubunitexpressioninatcelltransferbasedcolitismodel AT alicesijts enhancedinflammatorypotentialofcd4tcellsthatlackproteasomeimmunosubunitexpressioninatcelltransferbasedcolitismodel
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Enhanced inflammatory potential of CD4+ T-cells that lack proteasome immunosubunit expression, in a T-cell transfer-based colitis model.

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