ILC2s in High Definition: Decoding the Logic of Tissue-Based Immunity

Group 2 innate lymphoid cells (ILC2s) are widely distributed and are epigenetically poised for rapid type 2 effector function in response to a variety of tissue-derived signals. Developmental and precursor heterogeneity underlies highly dynamic, tissue-based mechanisms of ILC2 differentiation and function. Tissue microenvironments imprint ILC2 transcriptional profiles to encode receptivity to local cues, suggesting that communication between ILC2s and tissue niche cells is crucial to their function. ILC2–tissue cell circuits influence the cellular landscape in homeostasis and disease, providing a new understanding of tissue-based immune function. Group 2 innate lymphoid cells (ILC2s) mediate allergic immunity but have also recently come into focus as key sentinels of tissue health and homeostasis. Clues as to how these rare immune cells coordinate tissue-wide responses to perturbation have emerged from deciphering the communication between ILC2s and an ever-expanding list of diverse nonhematopoietic cells. High-resolution tracking and profiling approaches have accelerated these efforts, revealing ILC2 transcriptional programs that are coordinated with tissue and organism development. We propose that the engagement of these homeostatic feedback circuits by internal and external cues forms the basis for how tissues instruct type 2 immunity. Understanding how these normally restorative networks become unbalanced may be crucial in devising appropriately targeted therapies for allergic diseases. Group 2 innate lymphoid cells (ILC2s) mediate allergic immunity but have also recently come into focus as key sentinels of tissue health and homeostasis. Clues as to how these rare immune cells coordinate tissue-wide responses to perturbation have emerged from deciphering the communication between ILC2s and an ever-expanding list of diverse nonhematopoietic cells. High-resolution tracking and profiling approaches have accelerated these efforts, revealing ILC2 transcriptional programs that are coordinated with tissue and organism development. We propose that the engagement of these homeostatic feedback circuits by internal and external cues forms the basis for how tissues instruct type 2 immunity. Understanding how these normally restorative networks become unbalanced may be crucial in devising appropriately targeted therapies for allergic diseases. the outer layer of loosely organized connective tissue surrounding vessels or other tubular structures. endogenous molecules that signal cell or tissue damage to the immune system. a chronic inflammatory skin condition characterized by red, itchy, and cracked skin. an inflammatory disease of the mucosal tissues lining the nasal and sinus airspaces. a hallmark of chronic skin diseases such as atopic dermatitis: a complex physiologic circuit consisting of itch sensation and subsequent scratching behavior which self-perpetuates by exacerbating inflammatory and neural signals that trigger a reflex-like response. a low-calcemic vitamin D3 analog (also known as calcipotriol) that is administered topically to mice to induce atopic dermatitis-like allergic skin inflammation. a subset of CD4+ type 2 T helper (Th) cells in tissues that are characterized by high expression of the transcription factor GATA3 and production of the canonical type 2 immune cytokines IL-4, IL-5, and IL-13 which mediate many of the hallmarks of allergic inflammation, including tissue accumulation of eosinophils. substances that cause pruritus (itching). cells comprising the sebaceous glands that produce lipid-rich sebum. chemosensory epithelial cells that are characterized by a 'tuft' of microvilli projecting from the apical surface, that can produce IL-25, and are present in mucosal tissues such as the gastrointestinal and respiratory tracts in mammals. a physiologic response in mammals that is coordinated by type 2 immune signaling and is associated with the expulsion of helminths from intestinal tissues by increased smooth muscle contractility, mucus overproduction, and luminal fluid flow.