{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T21:09:44Z","timestamp":1790629784219,"version":"4.1.0"},"reference-count":33,"publisher":"Rockefeller University Press","issue":"10","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2015,9,21]]},"abstract":"<jats:p>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\u2013independent 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\u2013mediated 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.<\/jats:p>","DOI":"10.1084\/jem.20150303","type":"journal-article","created":{"date-parts":[[2015,8,25]],"date-time":"2015-08-25T01:13:54Z","timestamp":1440465234000},"page":"1487-1495","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":29,"title":["Cysteinyl leukotrienes mediate lymphokine killer activity induced by NKG2D and IL-15 in cytotoxic T cells during celiac disease"],"prefix":"10.1084","volume":"212","author":[{"given":"Fangming","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Medicine 1 , 2 , and 3"},{"name":"University of Chicago Celiac Disease Center 1 , 2 , and 3"},{"name":"Section of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of Chicago, Chicago, IL 60637 1 , 2 , and 3"},{"name":"Department of Medicine 1 , 2 , and 3"},{"name":"University of Chicago Celiac Disease Center 1 , 2 , and 3"},{"name":"Section of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of Chicago, Chicago, IL 60637 1 , 2 , and 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Sally","sequence":"additional","affiliation":[{"name":"Department of Medicine 1 , 2 , and 3"},{"name":"University of Chicago Celiac Disease Center 1 , 2 , and 3"},{"name":"Section of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of Chicago, Chicago, IL 60637 1 , 2 , and 3"},{"name":"Department of Medicine 1 , 2 , and 3"},{"name":"University of Chicago Celiac Disease Center 1 , 2 , and 3"},{"name":"Section of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of Chicago, Chicago, IL 60637 1 , 2 , and 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