Allergy Asthma Immunol Res.  2020 May;12(3):381-398. 10.4168/aair.2020.12.3.381.

Innate Lymphoid Cells in the Airways: Their Functions and Regulators

• Orimo K
• Saito H
• Matsumoto
• Morita H

• KMID: 2471224
• DOI: http://doi.org/10.4168/aair.2020.12.3.381

Abstract

Since the airways are constantly exposed to various pathogens and foreign antigens, various kinds of cells in the airways"”including structural cells and immune cells"”interact to form a precise defense system against pathogens and antigens that involve both innate immunity and acquired immunity. Accumulating evidence suggests that innate lymphoid cells (ILCs) play critical roles in the maintenance of tissue homeostasis, defense against pathogens and the pathogenesis of inflammatory diseases, especially at body surface mucosal sites such as the airways. ILCs are activated mainly by cytokines, lipid mediators and neuropeptides that are produced by surrounding cells, and they produce large amounts of cytokines that result in inflammation. In addition, ILCs can change their phenotype in response to stimuli from surrounding cells, which enables them to respond promptly to microenvironmental changes. ILCs exhibit substantial heterogeneity, with different phenotypes and functions depending on the organ and type of inflammation, presumably because of differences in microenvironments. Thus, ILCs may be a sensitive detector of microenvironmental changes, and analysis of their phenotype and function at local sites may enable us to better understand the microenvironment in airway diseases. In this review, we aimed to identify molecules that either positively or negatively influence the function and/or plasticity of ILCs and the sources of the molecules in the airways in order to examine the pathophysiology of airway inflammatory diseases and facilitate the issues to be solved.

Keyword

Respiratory tract diseases; innate immune response; cellular microenvironment; lymphocytes; phenotype; cytokines

MeSH Terms

Adaptive Immunity
Cellular Microenvironment
Cytokines
Homeostasis
Immunity, Innate
Inflammation
Lymphocytes*
Neuropeptides
Phenotype
Plastics
Population Characteristics
Respiratory Tract Diseases
Cytokines
Neuropeptides
Plastics

Figure

• 

  Fig. 1 Plasticity of ILCs in the airways. IL-4 induces conversion of ILC1s and ILC3s to ILC2s. IL-12, in conjunction with IL-1β or IL-18, induces conversion of ILC2s to ILC1s. IL-1β and IL-23, in conjunction with TGF-β, induce conversion of ILC2s to ILC3s. IL-1β and IL-23 also induce conversion of ILC1s to ILC3s in the intestines, but this has not been demonstrated in the airways. Retinoic acid, in conjunction with IL-33, induces conversion of ILC2s to ILCregs.ILC, innate lymphoid cell; ILC1, group 1 innate lymphoid cell; ILC2, group 2 innate lymphoid cell; ILC3, group 3 innate lymphoid cell; IL, interleukin; TGF-β, transforming growth factor-β; ILCreg, regulatory innate lymphoid cell; IFN, interferon; T-bet, T-box-expressed-in-T cells; RORγt, express retinoic acid receptor-related orphan receptor-γt; GATA3, GATA binding protein 3.

• 

  Fig. 2 Regulators of ILCs in the airways and their sources. In the airways, ILCs are regulated by various stimuli that are produced by other cells. The red arrows indicate stimuli that activate ILCs, and the blue ones indicate stimuli that suppress ILCs.ILC, innate lymphoid cell; ILC1, group 1 innate lymphoid cell; ILC2, group 2 innate lymphoid cell; ILC3, group 3 innate lymphoid cell; IL, interleukin; ILCreg, regulatory innate lymphoid cell; IFN, interferon; DC, dendritic cell; Th, T helper; Treg, regulatory T cell; SCC, solitary chemosensory cell; TSLP, thymic stromal lymphopoietin; CysLT, cysteinyl leukotriene; PGD2, prostaglandin D2; NMU, neuromedin U; VIP, vasoactive intestinal peptide; CGRP, calcitonin gene-related peptide; PNEC, pulmonary neuroendocrine cell.

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