NKR-P1B Receptor Expression and Function in the Different Innate Lymphoid Cells of the Lung

Abstract

Group 2 innate lymphoid cells (ILC2) are the majority of ILCs in murine lungs at steady state. ILC2s are the main producer of type-2-cytokines, IL-4, IL-5, IL-9, IL-13, and amphiregulin, playing key roles in lung tissue homeostasis, airway responses to pathogens and allergens, and in cancer-related defenses. ILC functions are regulated by cell surface receptors. NKR-P1B is an inhibitory receptor, which recognizes C-type lectin-related protein (Clr-b) as its ligand. NKR-P1B is expressed on subsets of natural killer cells, ILC2, ILC3, γδ T cells, macrophages and dendritic cells in a tissue-specific manner and regulates NK cell and ILC3 functions in the gut. Expression and function of NKR-P1B in the lung ILC populations is unexplored. Moreover, Clr-b, the ligand for NKR-P1B, is expressed in the bronchial epithelium, endothelial cells and in lung parenchyma, but its role in immune regulation in the lung is unknown. We hypothesize that ILC2s in the lung express NKR-P1B, and their function is regulated by the NKR-P1B:Clr-b recognition system. Using wild-type (WT) and NKR-P1B-deficient mice, we study the expression of NKR-P1B on lung ILC2, and the function of NKR-P1B:Clr-b recognition system in ILC2 development and function. We compare the phenotype, frequency, numbers and cytokine production by ILC2s upon stimulation between WT and NKR-P1B-deficient mice using antibody staining and flow cytometry analysis. This study will reveal the role of NKR-P1B as a model system for its human homolog, NKR-P1A, in the regulation of ILC development and function, advancing our understanding of how immune responses in the lung are regulated.