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  • 1
    Online Resource
    Online Resource
    Increased Interleukin-27 Production by Antigen-Presenting Cells Promotes Regulatory T Cell Differentiation and Contributes to Inducing a Remission in Patients with Eosinophilic Granulomatosis with Polyangiitis
    S. Karger AG ; 2013
    In:  International Archives of Allergy and Immunology Vol. 161, No. Suppl. 2 ( 2013), p. 66-74
    Details
    In: International Archives of Allergy and Immunology, S. Karger AG, Vol. 161, No. Suppl. 2 ( 2013), p. 66-74
    Abstract: 〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 We investigated the cytokine production profiles of antigen-presenting cells (APCs) and the status of patients with eosinophilic granulomatosis with polyangiitis (EGPA) in order to identify the cytokine profile that contributes to inducing differentiation of CD4 〈 sup 〉 + 〈 /sup 〉 effector Th cells and regulatory T cells. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 We counted the number of CD4 〈 sup 〉 + 〈 /sup 〉 FOXP3 〈 sup 〉 + 〈 /sup 〉 T cells, CD4 〈 sup 〉 + 〈 /sup 〉 CD25 〈 sup 〉 + 〈 /sup 〉 CTLA-4 〈 sup 〉 + 〈 /sup 〉 T cells, CD4 〈 sup 〉 + 〈 /sup 〉 T cells that predominantly produce IL-10 (Tr1 cells) and IL-17 (Th17 cells) and monocytes and monocyte-derived dendritic cells (mDCs) expressing Toll-like receptor (TLR)2 and TLR4 in the peripheral blood of 47 EGPA patients and 40 bronchial asthma patients (who did not have EGPA) and calculated the percentages of monocytes and mDCs that produced IL-23p19 and IL-27 in response to lipopolysaccharide (LPS) stimulation. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 Lower TLR4 expression was observed on the monocytes of relapsed EGPA patients and lower expression of both TLR2 and TLR4 on their mDCs than on the cells from EGPA patients in remission or non-EGPA patients. The percentages of monocytes expressing TLR4 were positively correlated with the percentages of regulatory T cells in peripheral blood. In addition, the percentages of monocytes and the percentages of mDCs that produced IL-27 and IL-23p19 in response to LPS stimulation were positively correlated with the percentages of Tr1 cells and Th17 cells in peripheral blood. A positive correlation was also found between the percentages of mDCs that produced IL-27 and the percentages of Tr1 cells. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 Increased dominancy of IL-23p19 and IL-27 production by the APCs of EGPA patients may be linked to differentiation of Th17 cells and Tr1 cells.
    Type of Medium: Online Resource
    ISSN: 1018-2438 , 1423-0097
    URL: Article
    DOI: 10.1159/000350645
    RVK:
    XA 49650
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2013
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  • 2
    Online Resource
    Online Resource
    Cytokine Production Profile of CD4+ T Cells from Patients with Active Churg-Strauss Syndrome Tends Toward Th17
    S. Karger AG ; 2009
    In:  International Archives of Allergy and Immunology Vol. 149, No. Suppl. 1 ( 2009), p. 61-65
    Details
    In: International Archives of Allergy and Immunology, S. Karger AG, Vol. 149, No. Suppl. 1 ( 2009), p. 61-65
    Abstract: 〈 i 〉 Background: 〈 /i 〉 Churg-Strauss syndrome (CSS) is a rare systemic necrotizing vasculitis that develops in some asthma patients. What types of asthma make patients prone to develop this condition remains unknown. We found that inhibition of regulatory T cells (Treg) differentiation, especially by Tr1 cells, due to a decreased ability of responder T cells to generate IL-2, is associated with the onset and pathogenesis of CSS. In contrast, recent evidence suggests that IL-17-producing Th17 cells play a crucial role in autoimmune inflammation. However, few studies have addressed the role of Th17 in the pathogenesis of CSS. 〈 i 〉 Methods: 〈 /i 〉 Mononuclear leukocytes were obtained from healthy subjects, patients with bronchial asthma (BA), asthma-accompanying chronic eosinophilic pneumonia (BA+CEP) and CSS. The cells were stimulated for 4–5 h with PMA and ionomycin in the presence of brefeldin A to generate and accumulate cytokines. Intracellular cytokines were detected after fixation and permeabilization of these cells. Tr1 cells were evaluated as CD4+CD25+ T cells dominantly producing IL-10 and TGF-β, nTreg as CD4+CD25+ T cells expressing Foxp3, a master transcriptional factor, and Th17 were also evaluated as CD4+ T cells mainly producing IL-17. Patients with CSS were classified into an active group and an inactive group in accordance with the disease state after treatment. 〈 i 〉 Results: 〈 /i 〉 The frequency of Th17 in peripheral blood was significantly higher in active CSS patients than in healthy subjects, BA, BA+CEP, and inactive CSS patients. In contrast, the Tr1 cell detection frequency was remarkably decreased in active CSS in comparison with BA, BA+CEP, and inactive CSS patients. Also, there was a significant relation between the condition of a given CSS patient and the detection frequencies of both CD4+ helper T cells when CSS cases were divided into inactive and active stages. The Th17 detection frequency was increased in the active stage of CSS, while the Tr1 frequency decreased sharply but then reversed in the inactive stage of CSS. 〈 i 〉 Conclusion: 〈 /i 〉 Active CSS patients have elevated intracellular IL-17 and decreased IL-10 levels, which correlate with measures of disease activity, suggesting that Th17 and Tr1 may play important roles in the pathogenesis of CSS.
    Type of Medium: Online Resource
    ISSN: 1018-2438 , 1423-0097
    URL: Article
    DOI: 10.1159/000210656
    RVK:
    XA 49650
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2009
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  • 3
    Online Resource
    Online Resource
    The Proportion of Regulatory T Cells in the Peripheral Blood Reflects the Relapse or Remission Status of Patients with Churg-Strauss Syndrome
    S. Karger AG ; 2011
    In:  International Archives of Allergy and Immunology Vol. 155, No. Suppl. 1 ( 2011), p. 46-52
    Details
    In: International Archives of Allergy and Immunology, S. Karger AG, Vol. 155, No. Suppl. 1 ( 2011), p. 46-52
    Abstract: 〈 i 〉 Background: 〈 /i 〉 Churg-Strauss syndrome (CSS) is a rare, systemic, necrotizing vasculitis that develops in some asthma patients. We previously reported that maintenance of the proportion of type 1 regulatory T (Tr1) cells in patients with chronic eosinophilic pneumonia and asthma might inhibit the development of CSS through the action of cytokines, such as interleukin (IL)-10 and IL-2, produced by Tr1 and responder T cells. We also reported that IL-17-producing CD4+ helper T cells (Th17 cells) are involved in the pathogenesis of CSS because a higher proportion of Th17 cells was observed in CSS patients during relapses than during remissions. However, few studies have addressed the role of both Tr1 cells and Th17 cells in the status of CSS. 〈 i 〉 Methods: 〈 /i 〉 We recruited 40 patients (25 in remission and 15 in relapse) for participation in this study. CSS was diagnosed on the basis of American College of Rheumatology criteria. Remission was defined as the absence of any clinical symptoms of active vasculitis. Tr1 cells were defined as CD4+CD25+ T cells that predominantly produce IL-10 when costimulated with phorbol myristate acetate (PMA) and ionomycin. Naturally occurring Treg (nTreg) cells were defined as CD4+CD25+ T cells that expressed Forkhead box P3 (FOXP3) and cytotoxic T-lymphocyte antigen 4 (CTLA-4). Th17 cells were identified as CD4+ T cells that mainly produced IL-17 and IL-22. Peripheral blood mononuclear cells (PBMCs) obtained from the subjects were costimulated with PMA and ionomycin, and intracellular cytokines were detected after fixing and permeabilizing the cells. Indoleamine 2,3-dioxygenase (IDO) expression was measured in PBMCs that had been treated with IFN-γ and then stimulated overnight with lipopolysaccharide (LPS) or lipopeptide Pam3CSK. 〈 i 〉 Results: 〈 /i 〉 Lower expression of CTLA-4 was observed on the surface of CD4+CD25+ T cells obtained from patients with relapsed CSS versus patients in remission. Both FOXP3-expressing nTreg cells and IL-10-producing Tr1 cells were detected in a lower proportion in patients with a relapse compared to patients in remission, but the proportion of CD4+ T cells producing IL-17 was higher during relapse than during remission. In addition, the proportion of CD4+ T cells that produced IL-25, which promotes Th2 inflammation, was also higher in the relapsed patients. We observed a lower percentage of CD14+ monocytes expressing both TLR2 and TLR4 obtained from patients with a relapse of CSS versus patients in remission. Stimulation of CD14+ monocytes with LPS or Pam3CSK reduced IDO expression by the cells from patients with relapsed CSS. The level of IDO expression was positively correlated with the proportion of Tr1 cells in the peripheral blood and inversely correlated with the percentage of Th17 cells. 〈 i 〉 Conclusion: 〈 /i 〉 CSS relapse may be linked to increased numbers of CD4+ T cells producing IL-25, which promotes Th2 inflammation, and to a decline in the Tr1 cell subpopulation resulting from lower IDO expression in monocytes. Thus, the proportions of Tr1 cells and Th17 cells reflect the status of CSS.
    Type of Medium: Online Resource
    ISSN: 1018-2438 , 1423-0097
    URL: Article
    DOI: 10.1159/000327265
    RVK:
    XA 49650
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2011
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  • 4
    Online Resource
    Online Resource
    Association between Temporary Housing Habitation after the 2011 Japan Earthquake and Mite Allergen Sensitization and Asthma Development
    S. Karger AG ; 2021
    In:  International Archives of Allergy and Immunology Vol. 182, No. 10 ( 2021), p. 949-961
    Details
    In: International Archives of Allergy and Immunology, S. Karger AG, Vol. 182, No. 10 ( 2021), p. 949-961
    Abstract: 〈 b 〉 〈 i 〉 Introduction: 〈 /i 〉 〈 /b 〉 We previously reported an increased prevalence of asthma in adults who lived in temporary housing after the 2011 Great East Japan Earthquake. The goal of the current study was to investigate changes in asthma prevalence and mite-specific immunoglobulin E (IgE) titers in temporary housing residents during 2014–2019. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 By using the Global Initiative for Asthma guidelines, we diagnosed asthma in Ishinomaki city temporary housing residents aged 15 years or older. We then analyzed serum antigen-specific IgE levels to 〈 i 〉 Dermatophagoides farinae 〈 /i 〉 ( 〈 i 〉 Der f 〈 /i 〉 ), 〈 i 〉 Dermatophagoides pteronyssinus 〈 /i 〉 ( 〈 i 〉 Der p 〈 /i 〉 ), and 〈 i 〉 Aspergillus fumigatus. 〈 /i 〉 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 The prevalence of asthma exceeded 20% across all age-groups throughout the study period. The proportion of study participants with a “positive” antigen-specific IgE titer (i.e., ≥0.35 IU 〈 sub 〉 A 〈 /sub 〉 /mL) was higher in asthmatics than in nonasthmatics for 〈 i 〉 Der f 〈 /i 〉 and 〈 i 〉 Der p 〈 /i 〉 but not for 〈 i 〉 Aspergillus fumigatus 〈 /i 〉 . Among residents ≥50 years old who were diagnosed with asthma, the percentage with a 〈 i 〉 Der f 〈 /i 〉 -specific IgE titer ≥0.10 IU 〈 sub 〉 A 〈 /sub 〉 /mL was higher than the proportion with ≥0.35 IU 〈 sub 〉 A 〈 /sub 〉 /mL. Among study participants, asthma onset occurred before the earthquake, during residence in shelters or temporary housing, and (starting in 2016) after moving out of temporary housing. The 〈 i 〉 Der p 〈 /i 〉 -specific IgE level was positively correlated with the duration of temporary housing ( 〈 i 〉 p 〈 /i 〉 & #x3c; 0.05, 〈 i 〉 r 〈 /i 〉 = 0.41) and inversely correlated with the time elapsed since moving out of temporary housing ( 〈 i 〉 p 〈 /i 〉 & #x3c; 0.05, 〈 i 〉 r 〈 /i 〉 = −0.35). 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 Mite allergen sensitization was found in both asthmatic and nonasthmatic temporary housing residents after the 2011 Japan earthquake and tsunami; asthma developed even after subjects moved out of temporary housing.
    Type of Medium: Online Resource
    ISSN: 1018-2438 , 1423-0097
    URL: Article
    DOI: 10.1159/000515870
    RVK:
    XA 49650
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2021
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  • 5
    Online Resource
    Online Resource
    Clinical Features of Patients with Active Eosinophilic Granulomatosis with Polyangiitis Successfully Treated with Mepolizumab
    S. Karger AG ; 2021
    In:  International Archives of Allergy and Immunology Vol. 182, No. 8 ( 2021), p. 744-756
    Details
    In: International Archives of Allergy and Immunology, S. Karger AG, Vol. 182, No. 8 ( 2021), p. 744-756
    Abstract: 〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 In some patients with eosinophilic granulomatosis with polyangiitis (EGPA), remission cannot be induced, despite treatment with corticosteroids and immunosuppressants. We evaluated the clinical features of patients with EGPA in whom mepolizumab was effective. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 There were 59 EGPA patients treated at Hiratsuka City Hospital, Japan, between April 2018 and September 2020, and 30 of them received mepolizumab. Twenty (66.7%) experienced a “marked effect” (the daily dose of corticosteroid or immunosuppressant could be decreased, or the interval between intravenous immunoglobulin (IVIG) treatments could be prolonged) and 10 (33.3%) experienced a “weak effect” (these measures were not achieved). Eosinophil numbers, serum IgG levels, daily doses of corticosteroids and immunosuppressants, and the interval between IVIG treatments at diagnosis and before and after mepolizumab initiation were determined. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 Eosinophil numbers at diagnosis were significantly higher in the marked-effect group than in the weak-effect group ( 〈 i 〉 p 〈 /i 〉 & #x3c; 0.05) but not before mepolizumab initiation or at the last visit. Birmingham Vasculitis Activity Scores (BVASs) before mepolizumab initiation ( 〈 i 〉 p 〈 /i 〉 & #x3c; 0.05) and at last visit ( 〈 i 〉 p 〈 /i 〉 & #x3c; 0.01), and frequency of relapse before treatment initiation ( 〈 i 〉 p 〈 /i 〉 & #x3c; 0.05) were significantly higher, and the serum IgG level before mepolizumab treatment was significantly lower in the weak-effect group than in the marked-effect group. The weak-effect group received higher doses of corticosteroids, even if the corticosteroid dose could be reduced for a while after mepolizumab initiation. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 High peripheral blood eosinophil numbers at EGPA diagnosis were suggestive of a positive clinical response to mepolizumab.
    Type of Medium: Online Resource
    ISSN: 1018-2438 , 1423-0097
    URL: Article
    DOI: 10.1159/000514505
    RVK:
    XA 49650
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2021
    detail.hit.zdb_id: 1482722-0
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