Characterization and Quantification of Innate Lymphoid Cell Subsets in Human Lung

Abstract

BackgroundInnate lymphoid cells (ILC) are a new family of innate immune cells that have emerged as important regulators of tissue homeostasis and inflammation. However, limited data are available concerning the relative abundance and characteristics of ILC in the human lung.MethodsThe aim of this study was to characterize and enumerate the different ILC subsets in human lung by multi-color flow cytometry.ResultsWithin the CD45+ Lin- CD127+ pulmonary ILC population, we identified group 1 (ILC1), group 2 (ILC2) and group 3 (ILC3) innate lymphoid cells using specific surface markers (i.e. IL12Rβ2, CRTH2 and CD117 respectively) and key transcription factors (i.e. T-bet, GATA-3 and RORγT respectively). Based on the presence of NKp44, ILC3 were further subdivided in natural cytotoxicity receptor (NCR)+ and NCR- ILC3. In addition, we demonstrated the production of signature cytokines IFN-γ, IL-5, IL-17A, IL-22 and GM-CSF in the pulmonary ILC population. Interestingly, we observed a tendency to a higher frequency of NCR- ILC3 in lungs of patients with chronic obstructive pulmonary disease (COPD) compared with controls.ConclusionsWe show that the three main ILC subsets are present in human lung. Importantly, the relative abundance of ILC subsets tended to change in COPD patients in comparison to control individuals.

Emerging roles of innate lymphoid cells in inflammatory diseases: Clinical implications

“…In patients with GOLD stage I and II, the ILC profile tended to shift toward IL-17-producing NKp44 À ILC3. 14 In a different study, GOLD stage IV patients had significantly more ILC3s and ILC1s, due to the differentiation of ILC2s into ILC1s. 6 Elevated ILC1 numbers were also found in peripheral blood of COPD patients, correlating with disease severity and susceptibility to exacerbations.…”

The Role of Lymphocytes in Radiotherapy-Induced Adverse Late Effects in the Lung

“…But, pathological conditions in the lung are associated with changes in the ILC population (96). In this context, ILC2 and ILC3 seem to play more imported roles than ILC1 during chronic lung disease in both, mice and men (94, 97, 98). For example, in patients with chronic obstructive pulmonary disease (COPD) ILC3 constitute the major population with 60% of all ILC, whereas ILC2 amount to 30% and ILC1 to 10% of the ILC (98).…”

“…In this context, ILC2 and ILC3 seem to play more imported roles than ILC1 during chronic lung disease in both, mice and men (94, 97, 98). For example, in patients with chronic obstructive pulmonary disease (COPD) ILC3 constitute the major population with 60% of all ILC, whereas ILC2 amount to 30% and ILC1 to 10% of the ILC (98). Of note, depletion of ILC2 reduced epithelial integrity, induced epithelial degeneration, and impaired lung functions during influenza virus infection highlighting a protective role of ILC2 for these processes (91).…”

Crosstalk between Innate Lymphoid Cells and Other Immune Cells in the Tumor Microenvironment

“…Breast cancer cell lines can then be injected/implanted and allowed to grow up into the recess created by the window, therefore allowing a surgery free method of imaging ILC3 behavior over the development of the tumor [111, 113, 114]. The use of this window method can be extended to imaging ILC3 in the lung using a technique developed by Looney et al [115] which, although terminal, can allow the studying of ILC3 and other target cells in a fully functional lung from chronic obstructive pulmonary disease [116] and lung cancer [98]. Taking advantage of current photo-switchable mouse models provides another tool to examine ILC3 function.…”