Innate lymphoid cells in asthma: when innate immunity comes in a Th2 flavor

Asthma is typically considered as an immunologic Th2 cell-mediated disease, a notion that is still inspiring many therapeutic strategies. In the past years, however, an innate immune cell type has been discovered in mice that resides in the mucosa and secretes the Th2 cytokines IL-13 and IL-5 in response to IL-33 and IL-25 released by a damaged epithelium. These cells [now named group 2 innate lymphoid cells (ILC2s)] are rare, systemically dispersed, long-lived, and exist in humans. Recent work shows that ILC2s are critical for the development of asthma and related phenotypes in mice. Their role in human asthma remains unknown.

This article reviews the most recent work that highlights ILC2s and the mechanisms underlying their critical role in experimental asthma. We also review the results of asthma therapeutic trials that targeted IL-13 and IL-5, the products of both Th2 cells and ILC2s.

Although the limited success of these trials is often quoted to dismiss the role of Th2 immunity as a whole, we propose that Th2 cytokines released by ILC2s may be critical for human asthma, but are not adequately neutralized because they are not readily accessible in peripheral tissues.