{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T00:41:21Z","timestamp":1768869681186,"version":"3.49.0"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2012,11,1]],"date-time":"2012-11-01T00:00:00Z","timestamp":1351728000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Cysteinyl leukotrienes (cys-LTs) can mediate Th2 immunity to the house dust mite, Dermatophagoides farinae, via the type 1 receptor CysLT1R on dendritic cells (DCs). However, the role of the homologous type 2 receptor CysLT2R in Th2 immunity is unknown. D. farinae sensitization and challenge of CysLT2R-deficient mice showed a marked augmentation of eosinophilic pulmonary inflammation, serum IgE, and Th2 cytokines. Wild-type (WT) mice sensitized by adoptive transfer of D. farinae-pulsed CysLT2R-deficient bone marrow-derived DCs (BMDCs) also had a marked increase in D. farinae-elicited eosinophilic lung inflammation and Th2 cytokines in restimulated hilar nodes. This response was absent in mice sensitized with D. farinae-pulsed BMDCs lacking leukotriene C4 synthase (LTC4S), CysLT1R, or both CysLT2R\/LTC4S, suggesting that CysLT2R negatively regulates LTC4S- and CysLT1R-dependent DC-mediated sensitization. CysLT2R-deficient BMDCs had increased CysLT1R-dependent LTD4-induced ERK phosphorylation, whereas N-methyl LTC4 activation of CysLT2R on WT BMDCs reduced such signaling. Activation of endogenously expressed CysLT1R and CysLT2R occurred over an equimolar range of LTD4 and N-methyl LTC4, respectively. Although the baseline expression of cell surface CysLT1R was not increased on CysLT2R-deficient BMDCs, it was upregulated at 24 h by a pulse of D. farinae, compared with WT or CysLT2R\/LTC4S-deficient BMDCs. Importantly, treatment with N-methyl LTC4 reduced D. farinae-induced CysLT1R expression on WT BMDCs. Thus, CysLT2R negatively regulates the development of cys-LT\u2013dependent Th2 pulmonary inflammation by inhibiting both CysLT1R signaling and D. farinae-induced LTC4S-dependent cell surface expression of CysLT1R on DCs. Furthermore, these studies highlight how the biologic activity of cys-LTs can be tightly regulated by competition between these endogenously expressed receptors.<\/jats:p>","DOI":"10.4049\/jimmunol.1201865","type":"journal-article","created":{"date-parts":[[2012,9,23]],"date-time":"2012-09-23T00:14:55Z","timestamp":1348359295000},"page":"4556-4565","source":"Crossref","is-referenced-by-count":34,"title":["Cysteinyl Leukotriene 2 Receptor on Dendritic Cells Negatively Regulates Ligand-Dependent Allergic Pulmonary Inflammation"],"prefix":"10.1093","volume":"189","author":[{"given":"Nora A","family":"Barrett","sequence":"first","affiliation":[{"name":"Department of Medicine, Harvard Medical School, Boston, MA 02115; and Division of Rheumatology, Immunology and Allergy, Brigham and Women\u2019s Hospital , Boston, MA 02115"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James M","family":"Fernandez","sequence":"additional","affiliation":[{"name":"Department of Medicine, Harvard Medical School, Boston, MA 02115; and Division of Rheumatology, Immunology and Allergy, Brigham and Women\u2019s Hospital , Boston, MA 02115"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akiko","family":"Maekawa","sequence":"additional","affiliation":[{"name":"Department of Medicine, Harvard Medical School, Boston, MA 02115; and Division of Rheumatology, Immunology and Allergy, Brigham and Women\u2019s Hospital , Boston, MA 02115"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Xing","sequence":"additional","affiliation":[{"name":"Department of Medicine, Harvard Medical School, Boston, MA 02115; and Division of Rheumatology, Immunology and Allergy, Brigham and Women\u2019s Hospital , Boston, MA 02115"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Medicine, Harvard Medical School, Boston, MA 02115; and Division of Rheumatology, Immunology and Allergy, Brigham and Women\u2019s Hospital , Boston, MA 02115"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew W","family":"Parsons","sequence":"additional","affiliation":[{"name":"Department of Medicine, Harvard Medical School, Boston, MA 02115; and Division of Rheumatology, Immunology and Allergy, Brigham and Women\u2019s Hospital , Boston, MA 02115"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K Frank","family":"Austen","sequence":"additional","affiliation":[{"name":"Department of Medicine, Harvard Medical School, Boston, MA 02115; and Division of Rheumatology, Immunology and Allergy, Brigham and Women\u2019s Hospital , Boston, MA 02115"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshihide","family":"Kanaoka","sequence":"additional","affiliation":[{"name":"Department of Medicine, Harvard Medical School, Boston, MA 02115; and Division of Rheumatology, Immunology and Allergy, Brigham and Women\u2019s Hospital , Boston, MA 02115"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2012,11,1]]},"reference":[{"key":"2025032409325644400_r1","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1126\/science.2820055","article-title":"Leukotrienes and lipoxins: structures, biosynthesis, and biological effects","volume":"237","author":"Samuelsson","year":"1987","journal-title":"Science"},{"key":"2025032409325644400_r2","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/j.jaci.2009.05.046","article-title":"The leukotriene E4 puzzle: finding the missing pieces and revealing the pathobiologic implications","volume":"124","author":"Austen","year":"2009","journal-title":"J. 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