Biomedical subjects

Yuki Yoshiura

Publications and source records attributed to Yuki Yoshiura.

3 recordsLinked to original sources

PubMed2005

Different roles of interleukin-10 in onset and resolution of asthmatic responses in allergen-challenged mice.

OBJECTIVE: Although interleukin (IL)-10 is an immunoregulatory cytokine produced by various cells including T cells, its precise role in asthma remains uncertain. The aim of this study was to investigate the role of IL-10 in experimental asthma using ovalbumin (OVA)-sensitized mice. METHODOLOGY: Mice were challenged with OVA aerosol, and airway responsiveness and inflammation were measured. OVA-specific IL-10-producing CD4+ T cells were counted from lung cells collected by enzymatic digestion and stimulated ex vivo with OVA. The effects of an anti-IL-10 antibody on airway responsiveness and inflammation were also evaluated. RESULTS: The OVA challenge caused airway hyperresponsiveness and eosinophilic inflammation. A significant increase in IL-10-producing CD4+ T cells was observed, mainly in the CD45RB(low) subset, for several days after the OVA challenge. Anti-IL-10 antibody treatment before the OVA challenge did not affect eosinophilic inflammation but significantly inhibited airway hyperresponsiveness 24 h after the OVA challenge. However, anti-IL-10 antibody treatment just before the last OVA challenge significantly attenuated the resolution of eosinophilic inflammation without affecting airway responsiveness 2 weeks after the OVA challenge. CONCLUSIONS: Intrinsic IL-10 may have a distinct role in the early and late phases of asthmatic responses. In the early phase, IL-10 induces airway hyperresponsiveness, while in the late phase IL-10 contributes to the resolution of eosinophilic inflammation.

Allergens↗

PubMed2004

Decrease of interleukin-10-producing T cells in the peripheral blood of severe unstable atopic asthmatics.

BACKGROUND: Although IL-10 is known as an immunoregulatory cytokine produced by various cells including T cells, its basic profile in atopic asthma remains uncertain. OBJECTIVE: The profiles of IL-10 production in circulating CD4+ T cells of atopic asthmatics were investigated with respect to clinical severity. METHODS: Forty atopic asthmatics were divided into three groups: mild, and severe but stable and severe unstable asthmatics. Eosinophils were counted in the peripheral blood and sputum, and exhaled nitric oxide was assessed. PBMCs were stimulated with or without anti-CD3 and anti-CD28 antibodies and then processed for detecting IL-10-producing CD4+ cells using flow cytometry. RESULTS: There was no difference in the eosinophil count in blood or sputum and in nitric oxide level among the three groups. IL-10-producing CD4+ cells were mainly detected in a CD45RO+ memory population. The frequency of IL-10-producing cells after stimulation was significantly lower in the severe unstable group compared to the mild group. In addition, the frequency of IL-10-producing cells in the severe unstable group was significantly lower than that in the severe stable group despite the fact that both groups received similar treatments with high-dose inhaled corticosteroids. The IL-10 production of CD4+CD45RO+ cells in response to dexamethasone did not differ among the three groups. CONCLUSIONS: IL-10-producing CD4+CD45RO+ cells in the peripheral blood are decreased in severe unstable asthmatics, which is not explained by the effect of high-dose inhaled corticosteroid medication.

Adult↗

PubMed2004

B7-DC regulates asthmatic response by an IFN-gamma-dependent mechanism.

B7-H1 (PD-L1) and B7-DC (PD-L2) are the ligands for programmed death-1 (PD-1), which is a member of the CD28/CTLA-4 family and has been implicated in peripheral tolerance. We investigated the roles of B7-H1 and B7-DC in a murine OVA-induced allergic asthma model. B7-H1 was constitutively expressed on dendritic cells, macrophages, B cells, and T cells in the lungs of naive mice, and its expression could be dramatically increased after allergen challenge. In contrast, B7-DC expression was scarcely expressed on dendritic cells in naive mice, but was up-regulated after allergen challenge, although the up-regulation of B7-DC expression on macrophages was minimal. Treatment of mice with anti-B7-DC mAb at the time of allergen challenge, but not at the time of sensitization, significantly increased their airway hyper-reactivity and eosinophilia. Such treatment also resulted in the increased production of IL-5 and IL-13, and decreased IFN-gamma production in the lungs and draining lymph node cells. These changes were diminished when mice were depleted of IFN-gamma by anti-IFN-gamma mAb pretreatment. Interestingly, treatment with anti-B7-H1 or anti-PD-1 mAb did not significantly affect the asthmatic response. These results suggest a unique role for B7-DC in the regulation of asthmatic response through an IFN-gamma-dependent, but PD-1-independent, mechanism.

Allergens↗