Pathogenic Th2-type follicular helper T cells contribute to the development of lupus in Fas-deficient mice.

Fas mutant mice are well recognized as autoimmune mouse models, which develop symptoms similar to human systemic lupus erythematosus. Although disease severity in Fas mutant mice is greatly affected by the genetic background, the mechanisms affecting pathological heterogeneity among different strains of Fas mutant mice are poorly understood. In this study, we examined the phenotypic differences between Fas-deficient (Fas (-/-)) mice on the BALB/c and C57BL/6 backgrounds to gain insight into the etiological and pathological heterogeneity of monogenic autoimmune diseases.

Identification of a novel type 2 innate immunocyte with the ability to enhance IgE production.

Fas (CD95), a member of the tumor necrosis factor receptor superfamily, mediates apoptosis-inducing signals in its expressing cells, especially in self-reactive cells. We recently reported that Fas(-/-) mice with a BALB/c background (BALB/c Fas(-/-) mice) developed blepharitis with allergic inflammation that was accompanied by hyper-IgE production. Here, we found a novel type of immunocyte in the spleen of BALB/c Fas(-/-) mice, which enhanced the production of IgE by B cells in the presence of IL-4 and CD40 signaling in vitro.

Fas deficiency in mice with the Balb/c background induces blepharitis with allergic inflammation and hyper-IgE production in conjunction with severe autoimmune disease.

Fas (CD95) is a cell surface death receptor belonging to the tumor necrosis factor receptor superfamily, which mediates apoptosis-inducing signaling when activated by Fas ligand or its agonistic antibody. lpr mice with a loss of apoptosis-inducing function mutation in the Fas gene develop systemic autoimmune disease and lymphadenopathy but not allergic inflammation. In the case of Fas mutations including lpr and knockout (KO), background genes determine the incidence and severity of lymphadenopathy and histopathological manifestation of systemic autoimmunity: MRL-lpr/lpr mice and C57BL/6-lpr/lpr or C57BL/6 Fas KO mice develop severe and minimum disease, respectively.

A critical role of IL-33 in experimental allergic rhinitis.

Background: We reported previously that serum levels of IL-33 are significantly increased in patients with allergic rhinitis (AR). However, very little is known about the role of IL-33 for the development of AR.

Objective: We thought to develop a novel murine model of ragweed pollen-specific AR and examined the pathologic role for ragweed-induced IL-33 in the development of AR manifestation using IL-33-deficient (il33(-/-)) mice.

Crucial role of impaired Kupffer cell phagocytosis on the decreased Sonazoid-enhanced echogenicity in a liver of a nonalchoholic steatohepatitis rat model.

Aims: To evaluate the dynamics of Kupffer cell (KC) phagocytosis by performing both in vivo and in vitro studies using Sonazoid (GE Healthcare, Oslo) in a rat nonalcoholic steatohepatitis (NASH) model.

Methods: Contrast enhanced ultrasonography (CEUS) was performed on a rat NASH model induced by a methionine choline deficient diet (MCDD) and control rats, and Sonazoid was used to measure the signal intensity in the liver parenchyma. The uptake of Sonazoid by the KCs was observed by intravital microscopy.

Contribution of IL-33 to induction and augmentation of experimental allergic conjunctivitis.

IL-33, a member of the IL-1 family of cytokines, is the ligand for ST2 (IL-33Ralpha chain). IL-33 has the capacity to induce T(h)2 cytokine production from T(h)2 cells, mast cells and basophils, indicating that IL-33 has the potential to induce T(h)2 cytokine-mediated allergic inflammation of the eye. Thus, we tested the pathological role of IL-33 in allergic conjunctivitis (AC).

Administration of IL-33 induces airway hyperresponsiveness and goblet cell hyperplasia in the lungs in the absence of adaptive immune system.

Systemic administration of IL-18 induces polyclonal IgE responses by causing NKT cells to express CD40 ligand and to produce IL-4. Administration of IL-33 also induces IgE response, although the mechanism underlying IgE response is unclear. Here, we compared the effects of IL-18 and IL-33 on bone marrow-derived mast cells and basophils as well as non-polarized and T(h)2-polarized CD4(+) T cells in vitro.

Critical roles of myeloid differentiation factor 88-dependent proinflammatory cytokine release in early phase clearance of Listeria monocytogenes in mice.

Listeria monocytogenes (LM), a facultative intracellular Gram-positive bacterium, often causes lethal infection of the host. In this study we investigated the molecular mechanism underlying LM eradication in the early phase of infection. Upon infection with LM, both IL-12 and IL-18 were produced, and then they synergistically induced IFN-gamma production, leading to normal LM clearance in the host.