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The Role of Group 3 Innate Lymphoid Cells in Lung Infection and Immunity.

ABSTRACT: The lung is constantly exposed to environmental particulates such as aeroallergens, pollutants, or microorganisms and is protected by a poised immune response. Innate lymphoid cells (ILCs) are a population of immune cells found in a variety of tissue sites, particularly barrier surfaces such as the lung and the intestine. ILCs play a crucial role in the innate immune system, and they are involved in the maintenance of mucosal homeostasis, inflammation regulation, tissue remodeling, and pathogen clearance. In recent years, group 3 innate lymphoid cells (ILC3s) have emerged as key mediators of mucosal protection and repair during infection, mainly through IL-17 and IL-22 production. Although research on ILC3s has become focused on the intestinal immunity, the biology and function of pulmonary ILC3s in the pathogenesis of respiratory infections and in the development of chronic pulmonary inflammatory diseases remain elusive. In this review, we will mainly discuss how pulmonary ILC3s act on protection against pathogen challenge and pulmonary inflammation, as well as the underlying mechanisms.

SUBMITTER: Yang D

PROVIDER: S-EPMC7947361 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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The Role of Group 3 Innate Lymphoid Cells in Lung Infection and Immunity.

Yang Dan D Guo Xinning X Huang Tingxuan T Liu Chuntao C

Frontiers in cellular and infection microbiology 20210225

The lung is constantly exposed to environmental particulates such as aeroallergens, pollutants, or microorganisms and is protected by a poised immune response. Innate lymphoid cells (ILCs) are a population of immune cells found in a variety of tissue sites, particularly barrier surfaces such as the lung and the intestine. ILCs play a crucial role in the innate immune system, and they are involved in the maintenance of mucosal homeostasis, inflammation regulation, tissue remodeling, and pathogen ...[more]

PMID: 33718260

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Project description:BACKGROUND:IL-17 plays a pathogenic role in asthma. ST2- inflammatory group 2 innate lymphoid cells (ILC2s) driven by IL-25 can produce IL-17, whereas ST2+ natural ILC2s produce little IL-17. OBJECTIVE:We characterized ST2+IL-17+ ILC2s during lung inflammation and determined the pathogenesis and molecular regulation of ST2+IL-17+ ILC2s. METHODS:Lung inflammation was induced by papain or IL-33. IL-17 production by lung ILC2s from wild-type, Rag1-/-, Rorcgfp/gfp, and aryl hydrocarbon receptor (Ahr)-/- mice was examined by using flow cytometry. Bone marrow transfer experiments were performed to evaluate hematopoietic myeloid differentiation primary response gene-88 (MyD88) signaling in regulating IL-17 production by ILC2s. mRNA expression of IL-17 was analyzed in purified naive ILC2s treated with IL-33, leukotrienes, and inhibitors for nuclear factor of activated T cells, p38, c-Jun N-terminal kinase, or nuclear factor ? light-chain enhancer of activated B cells. The pathogenesis of IL-17+ ILC2s was determined by transferring wild-type or Il17-/- ILC2s to Rag2-/-Il2rg-/- mice, which further induced lung inflammation. Finally, expression of 106 ILC2 signature genes was compared between ST2+IL-17+ ILC2s and ST2+IL-17- ILC2s. RESULTS:Papain or IL-33 treatment boosted IL-17 production from ST2+ ILC2s (referred to by us as ILC217s) but not ST2- ILC2s. Ahr, but not retinoic acid receptor-related orphan receptor ?t, facilitated the production of IL-17 by ILC217s. The hematopoietic compartment of MyD88 signaling is essential for ILC217 induction. IL-33 works in synergy with leukotrienes, which signal through nuclear factor of activated T-cell activation to promote IL-17 in ILC217s. Il17-/- ILC2s were less pathogenic in lung inflammation. ILC217s concomitantly expressed IL-5 and IL-13 but expressed little GM-CSF. CONCLUSION:During lung inflammation, IL-33 and leukotrienes synergistically induce ILC217s. ILC217s are a highly pathogenic and unexpected source for IL-17 in lung inflammation.

Dataset Information

The Role of Group 3 Innate Lymphoid Cells in Lung Infection and Immunity.

Publications

The Role of Group 3 Innate Lymphoid Cells in Lung Infection and Immunity.

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