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Tissue resident and migratory group 2 innate lymphoid cells in mice Mathae, Laura


Group 2 innate lymphoid cells (ILC2s) primarily reside on mucosal surfaces and produce copious amounts of IL-5 and IL-13 upon activation by epithelium-derived cytokines, such as IL-33, leading to inflammation characterized by eosinophilia. Elevated numbers of ILC2s are found in the peripheral blood of patients with allergic diseases including asthma, suggesting their involvement in the disease. Epidemiological studies have shown higher prevalence of asthma in women than men during reproductive age, but the mechanism is largely unknown. By using flow cytometric analyses, I found that post-pubertal female lung ILC2s are more responsive to IL-33 stimulation than male ILC2s. Gene expression analyses of purified ILC2s and measurement of epithelium-derived cytokines in the lung demonstrated ILC2 intrinsic and lung environmental differences between naïve female and male lungs, suggesting a more activated state of female ILC2s compared to male ILC2s at steady state conditions. ILC2s have previously been shown to be tissue resident at steady state as well as during inflammation. However, recent reports have demonstrated migratory potential of ILC2s upon activation. Intranasal IL-33 administration into mice caused expansion of ILC2s not only in the lung but also in the blood and liver. Parabiosis experiments showed that ILC2s migrate out of the lung to the liver through circulation. Lung-derived ILC2s potently produced IL-5, IL-13 and IL-6, inducing eosinophilia and mild fibrosis. In contrast, intranasal IL-33 pre-treatment attenuated concanavalin A-induced acute hepatitis and cirrhosis. Overall, these results highlight the complexity of ILC2 regulation and ILC2-mediated local and systemic immunity. These considerations need to be taken into account when investigating ILC2s in human diseases.

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