74 | wileyonlinelibrary.com/journal/imr Immunological Reviews. 2018;286:74–85. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd 1 | INTRODUCTION Innate lymphoid cells (ILCs) are a heterogeneous group of ef- fector cells capable of responding to environmental pathogens and potentially immunogenic triggers at the onset of inflamma- tion before the adaptive responses develop. Present through- out the human body and strategically enriched at mucosal sites, ILCs are thus an important innate source of effector cytokines secreted upon exposure to cytokines and mediators produced by epithelial, stromal, or other immune cells. 1 Their function is diverse and varies from controlling tissue and metabolic homeo- stasis, protecting from infectious diseases, but also contributing to the pathology of chronic inflammation and cancer. 2 Similar to other innate immune cells, ILCs rapidly respond to infection in an antigen-independent manner, since they lack somatic rearrange- ment of antigen receptors (TCR or BCR). On the other hand, their transcriptional and cytokine profiles do mirror those of T-helper cell subsets. Until recently, three major groups of ILCs have been recognized: group 1, 2, and 3; some consisting of one or multiple subsets. 3 However, the recent advances in our understanding of their transcriptional regulation, function, and their role in shaping the local tissues microenvironment have led to a re-evaluation of their categorization. 4 Therefore, ILCs are now subdivided into five subsets based on their development and function; natural killer (NK) cells, ILC1s, ILC2s, ILC3s, and lymphoid tissue inducer (LTi) cells. All ILC subsets, with the exception of NK cells, are characterized by the expression of the IL- 7Rα (CD127) and the absence of surface markers that define T cells, B cells and NK cells, myeloid cells, granulocytes, hematopoietic stem cells, and plasmacytoid dendritic cells, collectively defined as “lineage”. 3 Further characterization of ILC subsets is based on the expression of additional surface markers, transcription factors, and cyto- kines. Multiple studies show that, similar to T helper cells, mature ILC subsets can modify their phenotype and function based on environmental cues, a phenomenon named “plasticity” or “trans- differentiation”. 5–7 Plasticity differs fundamentally from devel- opment, which, by definition, involves the irreversible change of Received: 15 June 2018 | Accepted: 16 August 2018 DOI: 10.1111/imr.12708 INVITED REVIEW New insights into the function, development, and plasticity of type 2 innate lymphoid cells Lisette Krabbendam | Suzanne M. Bal | Hergen Spits | Korneliusz Golebski Department of Experimental Immunology, Amsterdam-UMC, Amsterdam, the Netherlands Correspondence Hergen Spits, Department of Experimental Immunology, Amsterdam-UMC, Amsterdam, The Netherlands. Email: hergen.spits@amc.uva.nl Summary Group 2 innate lymphoid cells (ILC2s) are the most well defined group of ILCs. ILC2 development is controlled by the GATA-3 transcription factor and these cells produce archetypal type 2 cytokines, such as IL-5 and IL-13. These cytokines mediate parasite expulsion and tissue repair, but also contribute to type 2 inflammatory diseases, includ- ing allergy, asthma and chronic rhinosinusitis with nasal polyps. In response to tightly regulated local environmental cues ILCs can generate characteristics of other sub- types, a process known as plasticity. Recent advances in the ILC2 field has led to the discovery that ILC2s can promptly shift to functional IFN- γ-producing ILC1s or IL-17- producing ILC3s, depending on the cytokines and chemokines produced by antigen presenting cells or epithelial cells. Due to yet unknown triggers, this complex network of signals may become dysregulated. In this review, we will discuss general ILC charac- teristic, ILC2 development, plasticity, memory function, and implications in disease. KEYWORDS ILC development, ILC pathology, ILC plasticity, type 2 inflammation, type 2 innate lymphoid cells This article is part of a series of reviews covering Innate Lymphoid Cells appearing in Volume 286 of Immunological Reviews.