Several studies have shown that IL-5 is important for eosinophil survival in both mice and humans. To determine the relevant sources of IL-5, the authors generated IL-5-reporter mice and used these animals to examine IL-5 expression in the steady state. They identified substantial populations of IL-5-producing cells in various resting tissues, including the brain, muscles, heart, skin, intestines, lungs and uterus, but found very few IL-5-producing cells in lymphoid tissues or in the liver. Closer analysis showed that the IL-5-expressing cells lacked lineage markers associated with conventional lymphocytes, but expressed surface markers associated with the ILC2 lineage.
In the lungs, IL-5-expressing ILC2s were detected in collagen-rich regions near airway-associated blood vessels. Experiments using IL-5 and IL-13 dual-reporter mice showed that ILC2s only expressed IL-5 and not IL-13 in the resting lungs, but upregulated their expression of both cytokines following helminth infection. By contrast, ILC2s in the small intestine constitutively expressed both IL-5 and IL-13. As IL-13 upregulates the expression of CC-chemokine ligand 11 (CCL11) and other molecules that are necessary for eosinophil recruitment, this may partly account for why eosinophils are found in the steady state in the small intestine but not in the lungs. Indeed, the authors used their IL-5-reporter mice to specifically deplete ILC2s from the lungs and found that this prevented the upregulation of CCL11 expression in response to type 2 inflammatory signals.
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