The Role of Innate Lymphoid Cells in Chronic Respiratory Diseases

Abstract

The lung is a vital mucosal organ that is constantly exposed to the external environment, and as such, its defenses are continuously under threat. The pulmonary immune system has evolved to sense and respond to these danger signals while remaining silent to innocuous aeroantigens. The origin of the defense system is the respiratory epithelium, which responds rapidly to insults by the production of an array of mediators that initiate protection by directly killing microbes, activating tissue-resident immune cells and recruiting leukocytes from the blood. At the steady-state, the lung comprises a large collection of leukocytes, amongst which are specialized cells of lymphoid origin known as innate lymphoid cells (ILCs). ILCs are divided into three major helper-like subsets, ILC1, ILC2 and ILC3, which are considered the innate counterparts of type 1, 2 and 17 T helper cells, respectively, in addition to natural killer cells and lymphoid tissue inducer cells. Although ILCs represent a small fraction of the pulmonary immune system, they play an important role in early responses to pathogens and facilitate the acquisition of adaptive immunity. However, it is now also emerging that these cells are active participants in the development of chronic lung diseases. In this mini-review, we provide an update on our current understanding of the role of ILCs and their regulation in the lung. We summarise how these cells and their mediators initiate, sustain and potentially control pulmonary inflammation, and their contribution to the respiratory diseases chronic obstructive pulmonary disease (COPD) and asthma.

Alarmins and innate lymphoid cells 2 activation: a common pathogenetic link connecting RSV bronchiolitis and later wheezing/asthma?

“…To maintain tissue homeostasis and integrity, lungs are protected by a complex network of highly specialized immune cells that include ILC [10,11]. Creating a first-line defense system, these cells play diverse roles in inflammation and infection, including promotion of innate immunity, acquisition of adaptive immunity, maintenance of epithelial barrier function and tissue repair [9][10][11]19]. Being tissue-resident elements, ILC tend to proliferate locally following environmental challenges [9][10][11]18].…”

“…Creating a first-line defense system, these cells play diverse roles in inflammation and infection, including promotion of innate immunity, acquisition of adaptive immunity, maintenance of epithelial barrier function and tissue repair [9][10][11]19]. Being tissue-resident elements, ILC tend to proliferate locally following environmental challenges [9][10][11]18]. However, there is increasing evidence that, in inflammatory disorders, ILC migrating from other organs could contribute to the expansion and the modulation of the local cell pools [19][20][21].…”

“…Based on distinctive phenotypic markers, transcription factors and effector function, ILC can be divided into three subsets: ILC1, ILC2 and ILC3. These ILC subsets share many phenotypic, morphological, and functional features with CD4 + Th1, Th2 and Th17 cells [9,10,[18][19][20][21]. However, in contrast with T-cells, regulated by antigen presentation via antigen-presenting cells, ILC are mainly regulated by soluble factors such as cytokines, chemokines, neuronal factors, and other inflammatory mediators [22][23][24][25].…”

“…These mediators include thymic stromal lymphopoietin (TSLP), IL-33, the high mobility group box 1 (HMGB1) and IL-25 [6,7]. Often characterized as "alarmins", these epithelial cell-derived proteins regulate a broad spectrum of immune cell populations and are particularly potent in eliciting and activating type 2 innate lymphoid cells (ILC2) in a variety of lung disorders, including RSV bronchiolitis and recurrent wheezing/asthma in childhood [7][8][9][10][11][12]. It is therefore possible that, following a first severe respiratory infection in early life, long-term epithelial cell progenitors or persistent epigenetic modifications leading to alarmin-induced ILC2 activation may be involved in the ongoing increased susceptibility to obstructive lung diseases [13].…”

Circulating Complement C1q as a Novel Biomarker is Associated with the Occurrence and Development of COPD

“…A large body of literature 3 , 4 has tested the hypothesis that COPD may be related to chronic inflammation, oxidative stress, protease antiprotease imbalance and other factors. Recent studies 5 , 6 have proposed that in addition to the above mechanisms, the immune response is also involved in COPD. Innate immunity, 7 acquired immunity, 7 T cell-mediated immune imbalance 8 , 9 and autoimmunity 10 play an important role in the pathogenesis of COPD.…”