Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Tang, Fangming, Sally, Benjamin, Lesko, Kathryn, Discepolo, Valentina, Abadie, Valerie, Ciszewski, Cezary, Semrad, Carol, Guandalini, Stefano, Kupfer, Sonia S., Jabri, Bana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2015
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
_version_ 1782391027580010496
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
work_keys_str_mv AT tangfangming cysteinylleukotrienesmediatelymphokinekilleractivityinducedbynkg2dandil15incytotoxictcellsduringceliacdisease
AT sallybenjamin cysteinylleukotrienesmediatelymphokinekilleractivityinducedbynkg2dandil15incytotoxictcellsduringceliacdisease
AT leskokathryn cysteinylleukotrienesmediatelymphokinekilleractivityinducedbynkg2dandil15incytotoxictcellsduringceliacdisease
AT discepolovalentina cysteinylleukotrienesmediatelymphokinekilleractivityinducedbynkg2dandil15incytotoxictcellsduringceliacdisease
AT abadievalerie cysteinylleukotrienesmediatelymphokinekilleractivityinducedbynkg2dandil15incytotoxictcellsduringceliacdisease
AT ciszewskicezary cysteinylleukotrienesmediatelymphokinekilleractivityinducedbynkg2dandil15incytotoxictcellsduringceliacdisease
AT semradcarol cysteinylleukotrienesmediatelymphokinekilleractivityinducedbynkg2dandil15incytotoxictcellsduringceliacdisease
AT guandalinistefano cysteinylleukotrienesmediatelymphokinekilleractivityinducedbynkg2dandil15incytotoxictcellsduringceliacdisease
AT kupfersonias cysteinylleukotrienesmediatelymphokinekilleractivityinducedbynkg2dandil15incytotoxictcellsduringceliacdisease
AT jabribana cysteinylleukotrienesmediatelymphokinekilleractivityinducedbynkg2dandil15incytotoxictcellsduringceliacdisease