Innate lymphoid cells and asthma

The recent discovery of innate lymphoid cells (ILCs) has changed our understanding of immune regulation and uncovers the importance of innate immunity in the development of asthma. Historically, asthma was thought to be a Th2 mediated disease of the adaptive immune system but it has recently become clear that there are several different phenotypes of asthma some of which are non-allergic. In their review, Yu et al discuss the various roles of ILCs in the immune system specific to different asthma phenotypes and other allergic diseases (J Allergy Clin Immunol 2014; 133(4): 943-950).

ILCs are lymphocytes that produce a variety of cytokines similar to CD4+ T cells, but are antigen non-specific, which allows them to function independently of adaptive immunity.  The authors explain that ILC1s are similar to Th1 cells and have been shown to inhibit eosinophilic airway inflammation by promoting eosinophil apoptosis. Several studies show the likeness of ILC2s to Th2 cells in that they produce Th2 cytokines IL-4, IL-5, and IL-13.  ILC2s are found in the lungs of mice and humans with airway hyper responsiveness (AHR) and in the skin of atopic dermatitis patients. Similar to Th17 cells, ILC3s producing IL-17 have been found in the lung of some asthma patients and in the gut of colitis patients, and have been proposed to be implicated in obesity induced asthma, based on studies in mice. 

The authors conclude that at least two of the three types of ILCs are likely to be involved in human asthma, and in regulating both inflammation and homeostasis. The discovery of ILCs also suggests that innate immunity profoundly shapes allergic disease, in the presence or absence of adaptive immunity. For example, while the markers of ILC2s are not fully understood, the ability of ILC2s to interact with other Th2 associated cell types involved in allergy shows promise for asthma research that may lead to improved therapies.

Question for the authors:

Could you elaborate further on how ILCs managed to elude scientists for so long?  

ILCs eluded scientists in the past because they do not express cell surface markers associated with adaptive lymphocytes (e.g., T cells and B cells).  In our zeal to understand adaptive lymphocytes, we gated out other lymphocytes (including ILCs) during flow cytometric analyses.  In effect, we “threw out the baby with the bath water.”