Article

Innate lymphoid cells - how did we miss them?

MRC Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 0QH, UK.
Nature Reviews Immunology (Impact Factor: 33.84). 01/2013; 13(2). DOI: 10.1038/nri3349
Source: PubMed

ABSTRACT Innate lymphoid cells (ILCs) are newly identified members of the lymphoid lineage that have emerging roles in mediating immune responses and in regulating tissue homeostasis and inflammation. Here, we review the developmental relationships between the various ILC lineages that have been identified to date and summarize their functions in protective immunity to infection and their pathological roles in allergic and autoimmune diseases.

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    • "These cytokines include TSLP, IL-4, IL-5, and IL-9, all classical Th2 polarizing cytokines, and all cytokines that significantly affect the development of pulmonary inflammation. Interestingly, this same population is capable of producing these same Th2 cytokines (IL-5, IL-9, and IL-13) in response to mice infected with helminthes, promoting an eosinophilic gut response and enhanced mucus production [85]. These derived innate lymphoid cells resemble Th2 polarized CD4 T cells but do not express an antigen specific receptor [86] [87] [88]. "
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    ABSTRACT: Asthma is a chronic inflammatory disease of the airways, resulting in bronchial hyperresponsiveness with every allergen exposure. It is now clear that asthma is not a single disease, but rather a multifaceted syndrome that results from a variety of biologic mechanisms. Asthma is further problematic given that the disease consists of many variants, each with its own etiologic and pathophysiologic factors, including different cellular responses and inflammatory phenotypes. These facets make the rapid and accurate diagnosis (not to mention treatments) of asthma extremely difficult. Protein biomarkers can serve as powerful detection tools in both clinical and basic research applications. Recent endeavors from biomedical researchers have developed technical platforms, such as cytokine antibody arrays, that have been employed and used to further the global analysis of asthma biomarker studies. In this review, we discuss potential asthma biomarkers involved in the pathophysiologic process and eventual pathogenesis of asthma, how these biomarkers are being utilized, and how further testing methods might help improve the diagnosis and treatment strain that current asthma patients suffer.
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    • "IL-5 plays an important role in the activation and recruitment of eosinophils to the airways, and IL-13 increases goblet cell hyperplasia , mucus production, and the sensitivity of airway smoothmuscle cells to stimuli and leads to airway hyperreactivity (AHR), a cardinal feature of asthma. Like Th2 cells, type 2 innate lymphoid cells (ILC2s) can rapidly produce large amounts of Th2 cytokines (Hazenberg and Spits, 2014; Walker et al., 2013) and therefore play an important role in the pathogenesis of asthma. ILC2s have been discovered as the source of IL-5 and IL-13 production in alymphoid, recombination activating gene (RAG)-deficient mice and can be activated by IL-25, IL-33, thymic stromal lymphopoietin (TSLP), and fungal allergens such as Alternaria. "
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    ABSTRACT: Allergic asthma is caused by Th2-cell-type cytokines in response to allergen exposure. Type 2 innate lymphoid cells (ILC2s) are a newly identified subset of immune cells that, along with Th2 cells, contribute to the pathogenesis of asthma by producing copious amounts of IL-5 and IL-13, which cause eosinophilia and airway hyperreactivity (AHR), a cardinal feature of asthma. ILC2s express ICOS, a T cell costimulatory molecule with a currently unknown function. Here we showed that a lack of ICOS on murine ILC2s and blocking the ICOS:ICOS-ligand interaction in human ILC2s reduced AHR and lung inflammation. ILC2s expressed both ICOS and ICOS-ligand, and the ICOS:ICOS-ligand interaction promoted cytokine production and survival in ILC2s through STAT5 signaling. Thus, ICOS:ICOS-ligand signaling pathway is critically involved in ILC2 function and homeostasis. Copyright © 2015 Elsevier Inc. All rights reserved.
    Immunity 03/2015; 42(3):538-552. DOI:10.1016/j.immuni.2015.02.007 · 19.75 Impact Factor
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    • "Group 2 ILCs include ILC2, also referred to as natural helper cells or nuocytes. ILC2 express CXCR4 and CCR9, which promote their homeostatic distribution (Walker et al. 2013). Using a CXCR6 reporter mouse, 50% of ILC2 was also shown to express the CXCR6 reporter (Roediger et al. 2013). "
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    ABSTRACT: Chemokines are chemotactic cytokines that control the migration and positioning of immune cells in tissues and are critical for the function of the innate immune system. Chemokines control the release of innate immune cells from the bone marrow during homeostasis as well as in response to infection and inflammation. They also recruit innate immune effectors out of the circulation and into the tissue where, in collaboration with other chemoattractants, they guide these cells to the very sites of tissue injury. Chemokine function is also critical for the positioning of innate immune sentinels in peripheral tissue and then, following innate immune activation, guiding these activated cells to the draining lymph node to initiate and imprint an adaptive immune response. In this review, we will highlight recent advances in understanding how chemokine function regulates the movement and positioning of innate immune cells at homeostasis and in response to acute inflammation, and then we will review how chemokine-mediated innate immune cell trafficking plays an essential role in linking the innate and adaptive immune responses. Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.
    Cold Spring Harbor perspectives in biology 01/2015; 7(5). DOI:10.1101/cshperspect.a016303 · 8.23 Impact Factor
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