Group 2 Innate Lymphoid Cells in Pulmonary Immunity and Tissue Homeostasis

Abstract

Group 2 innate lymphoid cells (ILC2) represent an evolutionary rather old but only recently identified member of the family of innate lymphoid cells and have received much attention since their detailed description in 2010. They can orchestrate innate as well as adaptive immune responses as they interact with and influence several immune and non-immune cell populations. Moreover, ILC2 are able to rapidly secrete large amounts of type 2 cytokines that can contribute to protective but also detrimental host immune responses depending on timing, location, and physiological context. Interestingly, ILC2, despite their scarcity, are the dominant innate lymphoid cell population in the lung, indicating a key role as first responders and amplifiers upon immune challenge at this site. In addition, the recently described tissue residency of ILC2 further underlines the importance of their respective microenvironment. In this review, we provide an overview of lung physiology including a description of the most prominent pulmonary resident cells together with a review of known and potential ILC2 interactions within this unique environment. We will further outline recent observations regarding pulmonary ILC2 during immune challenge including respiratory infections and discuss different models and approaches to study ILC2 biology in the lung.

The interaction of intestinal microbiota and innate lymphoid cells in health and disease throughout life

“…However, ILC2s can also support wound healing upon infection by the secretion of AREG in the respiratory tract as well as in the gut during inflammation, and thereby be beneficial for the host . Experimental factors might be involved in the different outcome of the ILC2 character including the use of different IAV subtypes in the studies, namely H3N1 and H1N1, or general variations in experimental procedures such as the different experimental time points analysed as previously discussed …”

“…126,129 Experimental factors might be involved in the different outcome of the ILC2 character including the use of different IAV subtypes in the studies, namely H3N1 and H1N1, or general variations in experimental procedures such as the different experimental time points analysed as previously discussed. 130,131 Antibiotic treatment influences not only the microbial composition in the gut (discussed above), but also has an important impact on ILC plasticity and function, 42 as well as on immunity to respiratory infections, such as influenza virus. 132 Here, reduced signalling via the inflammasome and TLRs leads to decreased activation and migration of DCs into the mediastinal lymph node.…”

Innate lymphoid cells in lung infection and immunity

“…ILC2 react to pathogens and challenge by sensing myeloid or epithelial cell‐derived cytokines and inflammatory mediators. In the respiratory milieu, myeloid cells, tuft cells, and epithelial cells provide the alarmins IL‐33, IL‐25, and thymic stromal lymphopoietin (TLSP), which act as potent activators of ILC2, leading to proliferation, GATA3 upregulation, and secretion of IL‐5 and IL‐13 . These effector cytokines mediate eosinophil recruitment, stimulate mucus production from goblet cells, affect smooth muscle contractility, and prime alveolar macrophages, all of which are functions associated with protection against helminth infections .…”

Airway-associated macrophages in homeostasis and repair

“…For example, at 1 and 3dpP we detected an increase in neutrophils, monocytes and macrophages. Neutrophils are thought to be key in modulating the cytokine environment to foster recruitment and differentiation of other immune players (Blázquez-Prieto et al, 2018;Kaplanski et al, 2003;Lechner et al, 2017;Mindt et al, 2018;Ricardo-Gonzalez et al, 2018). In the monocyte and macrophage compartment, we observed a shift toward M2-like polarization of macrophages.…”