NK cells participate in the development of human multiple sclerosis (MS) and mouse experimental autoimmune encephalomyelitis (EAE), but the roles of different NK cell subsets in disease onset remain poorly understood. In this study, murine NK cells were divided into CD27(high) and CD27(low/-) subsets. The CD27(high) subset was decreased and the CD27(low/-) subset was increased in lymphoid organs during the pre-onset stage of EAE. Compared with the counterpart in naïve mice, the CD27(high) subset showed lower expression of Ly49D, Ly49H and NKG2D, and less production of IFN-γ, whereas the CD27(low/-) subset showed similar expression of the above mentioned surface receptors but higher cytotoxic activity in EAE mice. Compared with the CD27(high) subset, the CD27(low/-) subset exhibited increased promotion of DC maturation and no significant inhibition of T cells proliferation and Th17 cells differentiation in vitro Additionally, adoptive transfer of the CD27(low/-) subset, but not the CD27(high) subset, exacerbated the severity of EAE. Collectively, our data suggest the CD27 NK cell subsets play different roles in controlling EAE onset, which provide a new understanding for the regulation of NK cell subsets in early autoimmune disease.

Basophils have been shown to contribute to anaphylaxis through either an IgE-FcεRI-dependent pathway or an IgG-FcγR pathway. However, it remains largely unclear whether basophils can be activated to promote anaphylaxis via a non-FcR pathway as well. The glycolipid receptor ASGM1 (Asialoganglioside gangliotetraosylceramide), which has an exposed GalNAcβ1-4Gal moiety and serves as a receptor for pathogen associated molecular patterns such as flagellin, was recently found to be expressed on basophils. Here, we demonstrate that stimulation of basophils with anti-ASGM1 antibodies promotes platelet-activating factor (PAF) secretion in vitro and in vivo. Moreover, we found that ASGM1 stimulation triggers basophil-and PAF-dependent anaphylactic shock in pertussis toxin (PTX)-pretreated mice. Thus, ASGM1 has a crucial role in basophil activation and basophil-mediated anaphylaxis-like shock in mice, especially when the vascular permeability is increased by PTX treatment. Our findings describe a novel anaphylaxisassociated pathway that is antigen-, antibody-, and FcR-independent.Keywords: Anaphylaxis r ASGM1 r Basophil r PAF Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionAnaphylaxis is a serious life-threatening allergic reaction characterized by rapid onset and potentially fatal outcomes [1]. The major manifestations of anaphylaxis include bronchoconstriction, pulmonary hypertension, systemic hypotension, and vascular leakage. A classical IgE-and FcεRI-dependent pathway has long been recognized to be associated with anaphylaxis. Binding of Correspondence: Dr. Fang Zheng e-mail: zhengfangtj@hust.edu.cn antigens to IgE and high-affinity cross-linking with FcεRI trigger the release of histamines from mast cells, resulting in anaphylaxis. Recently, various human and animal studies have indicated that IgG-and FcγR-involving pathways also mediate anaphylaxis in an IgE-independent fashion [2][3][4]. IgG antibodies, FcγRIIIA and FcγRIV, macrophages and neutrophils, as well as plateletactivating factor (PAF) are the main players in IgG-induced passive and active systemic anaphylaxis, in which IgE antibodies, FcεRI, mast cells, and histamine play a minor role [5]. It has been reported that in the absence of a specific allergen and antibodies, treatment with two injections of the cytokine IL-33 can trigger a third pathway for anaphylaxis in mice [6]. Kojimawww.eji-journal.eu Eur. J. Immunol. 2014. 44: 2468-2477 Innate immunity 2469 et al. also reported that in mice the anti-CD200R3 antibody Ba91 induced systemic and local anaphylaxis via an IgE-and IgG1-independent pathway that involved CD200R3 receptor activation [7]. Currently, it is largely unclear whether and how non-FcR receptors activate immune cells and trigger anaphylaxis. Basophils represent less than 1% of peripheral blood leukocytes. They are thought to contribute to anaphylaxis by releasing histamine and PAF. It has long been recognized that antigen binding to IgE and high-affinity cross-linkin...

Background: Natural killer (NK) cells are lymphocytes of the innate immune system that play a crucial role in tumor immune surveillance. Accumulated data indicated that NK cells in the tumor microenvironment often display a suppressed function. However, the mechanism is not clear. Objective: In this study, the effects and relative mechanisms of malignant pleural effusion (MPE) from patients with lung cancer on NK cells were researched. Methods: MPE and peripheral blood (PB) samples were collected from patients with lung cancer. The cytotoxic activity of CD56^dim NK cells in PB and MPE mononuclear cells was analyzed by flow cytometry. Results: It was observed that the percentages of total NK cells and a CD56^dim NK subset in MPE reduced accompanying impaired cytotoxic activity compared with that in paired PB. Cell-free MPE treatment reduced both the proportion and cytotoxic activity of CD56^dim NK cells in PB from healthy donors. The suppression effects were not based on soluble carcinoembryonic antigen and the inhibitory cytokines interleukin-10 and transforming growth factor-β₁, but were dependent on the factor with a molecular weight >100 kDa. Conclusions: These results demonstrated that native soluble carcinoembryonic antigen does not suppress the activity of NK cells, and an unknown factor with a molecular weight >100 kDa plays a critical role in the impairment of CD56^dim NK cells in MPE, which might lead to tumor progression.