TL1A induces TCR independent IL-6 and TNF-α production and growth of PLZF⁺ leukocytes.

An elevated level of the cytokine TL1A is known to be associated with several autoimmune diseases, e.g. rheumatoid arthritis and inflammatory bowel disease. However, the mode of action of TL1A remains elusive. In this study, we investigated the role of TL1A in a pro-inflammatory setting, using human...

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Autores principales:	Kirsten Reichwald, Tina Z Jørgensen, Peter Tougaard, Søren Skov
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6fd32b2082934b8994aea1b0789bcecf
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spelling	oai:doaj.org-article:6fd32b2082934b8994aea1b0789bcecf2021-11-18T08:38:21ZTL1A induces TCR independent IL-6 and TNF-α production and growth of PLZF⁺ leukocytes.1932-620310.1371/journal.pone.0085793https://doaj.org/article/6fd32b2082934b8994aea1b0789bcecf2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24416448/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203An elevated level of the cytokine TL1A is known to be associated with several autoimmune diseases, e.g. rheumatoid arthritis and inflammatory bowel disease. However, the mode of action of TL1A remains elusive. In this study, we investigated the role of TL1A in a pro-inflammatory setting, using human leukocytes purified from healthy donors. We show that TL1A, together with IL-12, IL-15 and IL-18, directly induces the production of IL-6 and TNF-α from leukocytes. Interestingly, TL1A-induced IL-6 was not produced by CD14⁺ monocytes. We further show that the produced IL-6 is fully functional, as measured by its ability to signal through the IL-6 receptor, and that the induction of IL-6 is independent of TCR stimulation. Furthermore, the transcription factor PLZF was induced in stimulated cells. These results offer a substantial explanation for the role of TL1A, since TNF-α and IL-6 are directly responsible for much of the inflammatory state in many autoimmune diseases. Our study suggests that TL1A is a possible target for the treatment of autoimmune diseases.Kirsten ReichwaldTina Z JørgensenPeter TougaardSøren SkovPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 1, p e85793 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kirsten Reichwald Tina Z Jørgensen Peter Tougaard Søren Skov TL1A induces TCR independent IL-6 and TNF-α production and growth of PLZF⁺ leukocytes.
description	An elevated level of the cytokine TL1A is known to be associated with several autoimmune diseases, e.g. rheumatoid arthritis and inflammatory bowel disease. However, the mode of action of TL1A remains elusive. In this study, we investigated the role of TL1A in a pro-inflammatory setting, using human leukocytes purified from healthy donors. We show that TL1A, together with IL-12, IL-15 and IL-18, directly induces the production of IL-6 and TNF-α from leukocytes. Interestingly, TL1A-induced IL-6 was not produced by CD14⁺ monocytes. We further show that the produced IL-6 is fully functional, as measured by its ability to signal through the IL-6 receptor, and that the induction of IL-6 is independent of TCR stimulation. Furthermore, the transcription factor PLZF was induced in stimulated cells. These results offer a substantial explanation for the role of TL1A, since TNF-α and IL-6 are directly responsible for much of the inflammatory state in many autoimmune diseases. Our study suggests that TL1A is a possible target for the treatment of autoimmune diseases.
format	article
author	Kirsten Reichwald Tina Z Jørgensen Peter Tougaard Søren Skov
author_facet	Kirsten Reichwald Tina Z Jørgensen Peter Tougaard Søren Skov
author_sort	Kirsten Reichwald
title	TL1A induces TCR independent IL-6 and TNF-α production and growth of PLZF⁺ leukocytes.
title_short	TL1A induces TCR independent IL-6 and TNF-α production and growth of PLZF⁺ leukocytes.
title_full	TL1A induces TCR independent IL-6 and TNF-α production and growth of PLZF⁺ leukocytes.
title_fullStr	TL1A induces TCR independent IL-6 and TNF-α production and growth of PLZF⁺ leukocytes.
title_full_unstemmed	TL1A induces TCR independent IL-6 and TNF-α production and growth of PLZF⁺ leukocytes.
title_sort	tl1a induces tcr independent il-6 and tnf-α production and growth of plzf⁺ leukocytes.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/6fd32b2082934b8994aea1b0789bcecf
work_keys_str_mv	AT kirstenreichwald tl1ainducestcrindependentil6andtnfaproductionandgrowthofplzfleukocytes AT tinazjørgensen tl1ainducestcrindependentil6andtnfaproductionandgrowthofplzfleukocytes AT petertougaard tl1ainducestcrindependentil6andtnfaproductionandgrowthofplzfleukocytes AT sørenskov tl1ainducestcrindependentil6andtnfaproductionandgrowthofplzfleukocytes
_version_	1718421505919942656

TL1A induces TCR independent IL-6 and TNF-α production and growth of PLZF⁺ leukocytes.

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