IL-33- and IL-25-responsive innate lymphoid cells are present in human peripheral blood. (P6237)

Recent advances in the initiation and maintenance of type 2 immune responses have highlighted a new cell type, the type 2 innate lymphoid cell (ILC2). Studies using mouse models show that ILC2s mediate helminth clearance in the gut and development of airway hyperresponsiveness in the lung. Further, the epithelium-derived cytokines IL-25 and IL-33 are integral to this process. However, how ILC2s contribute to chronic human airway diseases such as asthma and how IL-25 and IL-33 mediate that effect are not well characterized. Here we show that human peripheral blood mononuclear cells (PBMCs) respond to IL-33 or IL-25 stimulation by making IL-5 and IL-13. CD3+ and CD16+ PBMCs are not required. Furthermore, an ILC2-like cell that is lineage-negative and CD44+CD127+ST2+ is present in the peripheral blood of a subject with asthma. IL-5 production was induced by IL-33 or IL-25 in PBMCs from normal individuals as well as from patients with allergic rhinitis or allergic asthma, however, PBMCs from the group with asthma released significantly higher amounts. Our data suggests that the number and function of ILC2s is greater in patients with allergic asthma than in healthy subjects or patients with allergic rhinitis. Thus, ILC2s may be involved in the development of type 2 airway diseases.