Title:
Group 2 innate lymphoid cell and allergic disorders

Speaker:
Kazuyo Moro
Laboratory for Innate Immune Systems, RIKEN-IMS, Japan

Abstract:
Unlike T and B lymphocytes, ILCs lack antigen-specific receptors and are activated by cytokines produced by other innate immune cells or epithelial cells. ILCs have been divided into 3 groups based on their cytokine production profiles and group 2 innate lymphoid cells (ILC2s) are known to regulate type2 immune responses. ILC2s rapidly produce large amounts of IL-5 and IL-13, which are hallmark cytokines of Th2 cells, prior to the acquired immune response, suggesting that ILC2s regulate the initiation of allergic disorders. Although Th2 cells produce IL-4 as well as IL-5 and IL-13 after TCR stimulation by antigen, ILC2s fail to produce IL-4 even after stimulation with IL-33 or IL-25 which are known to induce IL-5 and IL-13 production by ILC2s. For this reason, ILC2s are not thought to contribute to IL-4-mediated immune responses.
In this study, we demonstrated that cysteinyl leukotrienes and neuropeptides initiate IL-4 production in ILC2s via calcium signaling, resulting in the production of antigen-nonspecific IgE from B1 cells. Polyclonal IgE induces the expansion of FcεR+ cells including basophils, eosinophils and mast cells in the periphery and augments ILC2-mediated lung inflammation during allergen challenge. Critically, a lack of ILC2s impairs the homeostasis of FcεR+ cells, resulting in resistance to allergic responses. Collectively, ILC2s, B1 cells, and FcεR+ cells comprise an amplification circuit that increases susceptibility to allergic inflammation in response to risk factors for allergies.