Abstract
The lungs represent a complex immune setting, balancing external environmental signals with a poised immune response that must protect from infection, mediate tissue repair, and maintain lung function. Innate lymphoid cells (ILCs) play a central role in tissue repair and homeostasis, and mediate protective immunity in a variety of mucosal tissues, including the lung. All three ILC subsets are present in the airways of both mice and humans; and ILC2s shown to have pivotal roles in asthma, airway hyper-responsiveness, and parasitic worm infection. The involvement of ILC3s in respiratory diseases is less well-defined, but they are known to be critical in homeostasis, infection and inflammation at other mucosal barriers, such as the gut. Moreover, they are important players in the IL17/IL22 axis, which is key to lung health. In this review, we discuss the emerging role of ILC3s in the context of infectious and inflammatory lung diseases, with a focus on data from human subjects.
Highlights
The lungs are complex organs, the proper functioning of which is essential for good health, but whose exposure to the external environment renders them susceptible to infections and environmental toxins
ILC1s are classically associated with the immune response to viral infection and tumor cells, while ILC2s are often compared to CD4+ Th2 cells and mediate the response to helminth infections and allergies
This study described a positive feedback loop in which TNFproducing monocytes recruited to lungs drove an increase in IL17-secreting Innate lymphoid cells (ILCs), which in turn enhanced monocyte-mediated bacterial uptake and killing
Summary
The lungs are complex organs, the proper functioning of which is essential for good health, but whose exposure to the external environment renders them susceptible to infections and environmental toxins. The lung immune environment must strike a delicate balance between dealing with this constant assault, whilst preventing immune mediated damage This results in an intricate immune setting that is still not completely understood [1], but which growing evidence suggests includes an important role for innate lymphoid cells (ILCs). ILCs mediate protective immunity from pathogens and promote tissue repair and homeostasis following infection, but may play a role in pathogenesis when their functions become dysregulated [2,3,4]. While all three ILC subsets have been identified in the airways, the majority of studies to date have focused on ILC2s, highlighting their importance in tissue repair, protection from helminth infections, and involvement in multiple allergic diseases [3, 11, 12]. The importance of ILCs as a source of GM-CSF in the lung remains untested, ILC3s in the gut are known to orchestrate inflammation through its activity [6]
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