Nuocyte

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.

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.

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.

Abstract: Activation and differentiation of the Th1 cell population lead to their production of the classical type-1 cytokines IFN-γ, IL-2, and TNF-β, thus promoting type-1 immunity. This is thought to occur via the ligation of TLRs by bacterial and viral products, which in turn, drive production of the essential Th1 cell differentiation factor, IL-12, by dendritic cells (DCs). Concurrent studies have been able to identify the effector cytokines produced by Th2 cells (IL-4, IL-5, IL-9, and IL-13) as being essential for parasitic immunity and also as essential factors in allergic asthma. However, the factors that are critical for initiation of the type-2 response remained obscure. Recently however, two critical observations have led to a more detailed understanding of the innate type-2 response. First, two novel, type-2-inducing cytokines-IL-25 and IL-33-were identified as being necessary for the up-regulation of the type-2 effector cytokines, mirroring the role of IL-12 in the type-1 response. Second, studies focused on target cell populations of IL-25 and IL-33 have identified novel, innate cell populations, which potentially bridge the gap between presentation of the type-2-inducing cytokine and the later adaptive Th2 cell response. In this review, we will discuss these new type-2 innate cell populations, in particular, the recently discovered nuocyte population, which are required for type-2 responses against helminthic parasites.