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Cysteinyl leukotrienes mediate lymphokine killer activity induced by NKG2D and IL-15 in cytotoxic T cells during celiac disease
Eicosanoids are inflammatory mediators that play a key but incompletely understood role in linking the innate and adaptive immune systems. Here, we show that cytotoxic effector T cells (CTLs) are capable of both producing and responding to cysteinyl leukotrienes (CystLTs), allowing for the killing o...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4577841/ https://www.ncbi.nlm.nih.gov/pubmed/26304964 http://dx.doi.org/10.1084/jem.20150303 |
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author | Tang, Fangming Sally, Benjamin Lesko, Kathryn Discepolo, Valentina Abadie, Valerie Ciszewski, Cezary Semrad, Carol Guandalini, Stefano Kupfer, Sonia S. Jabri, Bana |
author_facet | Tang, Fangming Sally, Benjamin Lesko, Kathryn Discepolo, Valentina Abadie, Valerie Ciszewski, Cezary Semrad, Carol Guandalini, Stefano Kupfer, Sonia S. Jabri, Bana |
author_sort | Tang, Fangming |
collection | PubMed |
description | Eicosanoids are inflammatory mediators that play a key but incompletely understood role in linking the innate and adaptive immune systems. Here, we show that cytotoxic effector T cells (CTLs) are capable of both producing and responding to cysteinyl leukotrienes (CystLTs), allowing for the killing of target cells in a T cell receptor–independent manner. This process is dependent on the natural killer receptor NKG2D and exposure to IL-15, a cytokine induced in distressed tissues. IL-15 and NKG2D signaling drives the up-regulation of key enzymes implicated in the synthesis of CystLTs, as well as the expression of CystLT receptors, suggesting a positive feedback loop. Finally, although the CystLT pathway has been previously linked to various allergic disorders, we provide unexpected evidence for its involvement in the pathogenesis of celiac disease (CD), a T helper 1 cell–mediated enteropathy induced by gluten. These findings provide new insights into the cytolytic signaling pathway of NKG2D and the pathogenesis of organ-specific immune disorders. Furthermore, they suggest that the blockade of CystLT receptors may represent a potent therapeutic target for CD or potentially other autoimmune disorders in which NKG2D has been implicated. |
format | Online Article Text |
id | pubmed-4577841 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-45778412016-03-21 Cysteinyl leukotrienes mediate lymphokine killer activity induced by NKG2D and IL-15 in cytotoxic T cells during celiac disease Tang, Fangming Sally, Benjamin Lesko, Kathryn Discepolo, Valentina Abadie, Valerie Ciszewski, Cezary Semrad, Carol Guandalini, Stefano Kupfer, Sonia S. Jabri, Bana J Exp Med Brief Definitive Report Eicosanoids are inflammatory mediators that play a key but incompletely understood role in linking the innate and adaptive immune systems. Here, we show that cytotoxic effector T cells (CTLs) are capable of both producing and responding to cysteinyl leukotrienes (CystLTs), allowing for the killing of target cells in a T cell receptor–independent manner. This process is dependent on the natural killer receptor NKG2D and exposure to IL-15, a cytokine induced in distressed tissues. IL-15 and NKG2D signaling drives the up-regulation of key enzymes implicated in the synthesis of CystLTs, as well as the expression of CystLT receptors, suggesting a positive feedback loop. Finally, although the CystLT pathway has been previously linked to various allergic disorders, we provide unexpected evidence for its involvement in the pathogenesis of celiac disease (CD), a T helper 1 cell–mediated enteropathy induced by gluten. These findings provide new insights into the cytolytic signaling pathway of NKG2D and the pathogenesis of organ-specific immune disorders. Furthermore, they suggest that the blockade of CystLT receptors may represent a potent therapeutic target for CD or potentially other autoimmune disorders in which NKG2D has been implicated. The Rockefeller University Press 2015-09-21 /pmc/articles/PMC4577841/ /pubmed/26304964 http://dx.doi.org/10.1084/jem.20150303 Text en © 2015 Tang et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Brief Definitive Report Tang, Fangming Sally, Benjamin Lesko, Kathryn Discepolo, Valentina Abadie, Valerie Ciszewski, Cezary Semrad, Carol Guandalini, Stefano Kupfer, Sonia S. Jabri, Bana Cysteinyl leukotrienes mediate lymphokine killer activity induced by NKG2D and IL-15 in cytotoxic T cells during celiac disease |
title | Cysteinyl leukotrienes mediate lymphokine killer activity induced by NKG2D and IL-15 in cytotoxic T cells during celiac disease |
title_full | Cysteinyl leukotrienes mediate lymphokine killer activity induced by NKG2D and IL-15 in cytotoxic T cells during celiac disease |
title_fullStr | Cysteinyl leukotrienes mediate lymphokine killer activity induced by NKG2D and IL-15 in cytotoxic T cells during celiac disease |
title_full_unstemmed | Cysteinyl leukotrienes mediate lymphokine killer activity induced by NKG2D and IL-15 in cytotoxic T cells during celiac disease |
title_short | Cysteinyl leukotrienes mediate lymphokine killer activity induced by NKG2D and IL-15 in cytotoxic T cells during celiac disease |
title_sort | cysteinyl leukotrienes mediate lymphokine killer activity induced by nkg2d and il-15 in cytotoxic t cells during celiac disease |
topic | Brief Definitive Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4577841/ https://www.ncbi.nlm.nih.gov/pubmed/26304964 http://dx.doi.org/10.1084/jem.20150303 |
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