At the bench: understanding group 2 innate lymphoid cells in disease

The conventional paradigm of type 2 inflammatory responses is characterized by activation of CD4(+) Th2 cells that produce IL-4, IL-5, and IL-13, resulting in tissue eosinophil infiltration, mucus metaplasia, AHR, and IgE production. However, the recent discovery of ILC2s in mice and humans has brought forth a novel pathway in type 2 immunity that may work independent of, or in concert with, adaptive Th2 responses. ILC2s were described initially as lineage-negative lymphocytes that produce high levels of Th2 cytokines IL-5 and IL-13 in response to IL-25 and IL-33 and promote protection against helminth infections. More recent investigations have identified novel upstream regulators, as well as novel ILC2 products. ILC2s are found in mucosal surfaces, including respiratory tract and skin, and studies from experimental asthma and atopic dermatitis models support a role for ILC2s in promoting type 2 inflammatory responses. There are many unanswered questions about the role of ILC2s in chronic allergic diseases, including how ILC2s or upstream pathways can be targeted for therapy. As ILC2s are not antigen specific and may be activated after exposures to a variety of infectious agents and irritants thought to contribute to respiratory and skin diseases, future strategies to target ILC2 function in human disease may be promising. Our intent is to identify priority areas for ILC2 translational research based on basic research insights.