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.
Highlights
Group 2 innate lymphoid cells (ILC2) have been identified less than a decade ago and constitute a new member of the family of innate lymphoid cells [1,2,3]
The indication of an innate lymphoid cell population linked to a type 2 immune response was first made in the 2000s: in mice, an IL-25-inducible non-T non-B cell population was reported to release large amounts of IL-5 and IL-13 [5], and in humans, a CD34+ population expressing both, IL-33R and TSLPR, was identified and shown to secrete type 2 signature cytokines upon stimulation with IL-33 or in combination with TSLP [6]
The recently identified nILC2 and iILC2 in the lungs are both induced upon N. brasiliensis infection albeit with different kinetics: iILC2 are induced early on and nILC2 are dominant in the lungs at late timepoints post infection, suggesting that iILC2 may act as transient progenitors of nILC2 in this setting [43]
Summary
Group 2 innate lymphoid cells (ILC2) have been identified less than a decade ago and constitute a new member of the family of innate lymphoid cells [1,2,3]. Despite the identification of ILC2 in various anatomical sites such as adipose tissue, liver, mesenteric lymph nodes (LNs), and the small intestinal lamina propria, Microenvironment and Immune Responses of Pulmonary ILC2 common characteristics of ILC2 became apparent from these early studies Those include their cytokine receptor expression profile, signature cytokines that are released, as well as their characteristic transcription factors. The delivery of inhaled air through this conduit, which may be loaded with potential antigens, allergens, and pathogens, is controlled by mechanical filters, physiological barriers, active expel, and immune defense mechanisms [18] These tasks are accomplished by the interaction and interplay of approximately 40 distinct cell populations in the lungs [19]. The well-organized and delicate structure of our respiratory immune system and its immediate surrounding is a unique microenvironment for ILC2
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