Nuocyte

About: Nuocyte is a research topic. Over the lifetime, 15 publications have been published within this topic receiving 2898 citations.

Nuocytes represent a new innate effector leukocyte that mediates type-2 immunity

Abstract: Innate immunity provides the first line of defence against invading pathogens and provides important cues for the development of adaptive immunity. Type-2 immunity-responsible for protective immune responses to helminth parasites and the underlying cause of the pathogenesis of allergic asthma-consists of responses dominated by the cardinal type-2 cytokines interleukin (IL)4, IL5 and IL13 (ref. 5). T cells are an important source of these cytokines in adaptive immune responses, but the innate cell sources remain to be comprehensively determined. Here, through the use of novel Il13-eGFP reporter mice, we present the identification and functional characterization of a new innate type-2 immune effector leukocyte that we have named the nuocyte. Nuocytes expand in vivo in response to the type-2-inducing cytokines IL25 and IL33, and represent the predominant early source of IL13 during helminth infection with Nippostrongylus brasiliensis. In the combined absence of IL25 and IL33 signalling, nuocytes fail to expand, resulting in a severe defect in worm expulsion that is rescued by the adoptive transfer of in vitro cultured wild-type, but not IL13-deficient, nuocytes. Thus, nuocytes represent a critically important innate effector cell in type-2 immunity.

Transcription factor RORα is critical for nuocyte development

Abstract: Nuocytes are innate cells with critical roles during infection with parasitic worms. McKenzie and colleagues show that nuocytes differentiate from common lymphoid progenitors and require IL-7, IL-33, Notch and RORα for development.

Increased expression of immunoreactive thymic stromal lymphopoietin in patients with severe asthma

Abstract: Background Thymic stromal lymphopoietin (TSLP) is a cytokine implicated in the pathophysiology of asthma through 2 distinct pathways: a TSLP–OX40 ligand (OX40L)–T cell axis and a TSLP–mast cell axis. Whether these pathways are active in human asthma is unknown. Objective We sought to investigate whether mucosal TSLP protein expression relates to asthma severity and distinct immunologic pathways. Methods In healthy subjects and patients with mild-to-severe asthma, we immunostained bronchial biopsy specimens for TSLP, OX40, OX40L, T H 2 cytokines, and inflammatory cell markers. We examined gene expression using RNA microarrays and quantitative RT-PCR. Results There was considerable heterogeneity in the levels of TSLP, IL-13, and IL-4 immunostaining across the cohort of asthmatic patients examined. Overall, TSLP protein expression was significantly increased in airway epithelium and lamina propria of asthmatic patients, particularly in patients with severe asthma. TSLP immunostaining in both compartments correlated with the severity of airflow obstruction. The majority of leukocytes expressing IL-13 were possibly nuocytes. Accounting for intersubject variability, the 55% of asthmatic patients with increased IL-13 immunostaining in the lamina propria also had increased IL-4 and TSLP expression. This was further substantiated by significant correlations between TSLP gene expression, a T H 2 gene expression signature, and eosinophilic inflammation in bronchial biopsy specimens. Immunostaining for OX40, OX40L, and CD83 was sparse, with no difference between asthmatic patients and healthy subjects. Conclusion TSLP expression is increased in a subset of patients with severe asthma in spite of high-dose inhaled or oral corticosteroid therapy. Targeting TSLP might only be efficacious in the subset of asthma characterized by increased TSLP expression and T H 2 inflammation.

Blocking IL-25 signalling protects against gut inflammation in a type-2 model of colitis by suppressing nuocyte and NKT derived IL-13.

Abstract: Background Interleukin-25 (IL-25) is a potent activator of type-2 immune responses. Mucosal inflammation in ulcerative colitis is driven by type-2 cytokines. We have previously shown that a neutralizing anti-IL-25 antibody abrogated airways hyperreactivity in an experimental model of lung allergy. Therefore, we asked whether blocking IL-25 via neutralizing antibodies against the ligand or its receptor IL-17BR could protect against inflammation in an oxazolone-induced mouse model of colitis.

Role of Innate Lymphocytes in Infection and Inflammation

Abstract: Cooperation of innate and adaptive immune responses is critical for the protective immunity against various invading microbes. Distinct types of effector T cells play different roles in adaptive immune responses. Th1 cells play important role in the control of intracellular bacteria by producing IFN-γ to activate macrophages. Th1 cells are also important in anti-viral immunity by producing IFN-γ and activating cytotoxic T lymphocytes. Th2 cell-derived cytokines are important in activating mast cells, eosinophils and goblet cells in anti-helminth immunity. Th17 cells are pivotal for the inflammatory response mediated by neutrophils to fight against extracellular bacterial infection. In all cases, it is critical to limit the growth and expansion of invading microbes by innate immune responses until antigen-specific adaptive immune responses are established. Recent studies have identified multiple subsets in innate lymphocyte corresponding to Th subsets. cNK cells, RORγ+ LTi-related cells and Th2-type innate lymphocytes play distinct roles in innate immune responses by producing Th1, Th17 and Th2 cytokines, respectively. Cooperation between those innate lymphocytes and antigen-specific T and B cells are likely important in protective immunity against distinct types of microbes. Most recently identified subset is RORγ-independent Lin-Thy-1+IL-7R+GATA3+ innate lymphocyte subset, which is Id2- and IL-7-dependent. This population is capable of producing Th2 cytokines, most notably IL-5 and IL-13, and plays a major role in the innate immune responses during anti-helminth immunity. In addition, these cells are likely involved in pathophysiology of some types of allergic diseases. We summarize here current knowledge about various innate lymphocyte subsets. In particular, we focus on the Th2-type innate lymphocyte subset.