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Type 2 Innate Lymphoid Cell Activation by Cysteinyl Leukotrienes : : a Novel Mechanism of Lipid-Mediated Allergic Inflammation


Type 2 innate lymphoid cells (ILC2) are a novel population of innate lymphocytes lacking expression of lineage markers. ILC2 lack antigen specificity and are instead activated by epithelial cytokines IL-33 and IL-25. Similar to type 2 T helper cells, ILC2 produce IL-5 and IL-13, two cytokines shown to be important in the development and pathology of asthma. Cysteinyl leukotrienes are important inflammatory mediators and potent bronchoconstrictors derived from arachidonic acid. 5-lipoxygenase converts arachidonic acid into leukotriene A4 (LTA4) and LTC4 synthase subsequently generates the cysteinyl leukotrienes, LTC4, LTD4, and LTE4. Expression of the cysteinyl leukotriene receptor 1 (CysLT1R) on ILC2 was shown both by flow cytometric analysis and PCR of sorted ILC2. Leukotriene C4, D4, and E4 administered intranasally induced ILC2 activation in vivo, and leukotriene D4 induced ILC2 IL-4, IL-5, and IL-13 production in vitro. Here, we show that the cysteinyl leukotrienes play a role as regulators and activators of type 2 innate lymphoid cells apart from known roles in bronchoconstriction and activation of other inflammatory cells

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