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Cytotoxic Tph-like cells are involved in persistent tissue damage in IgG4-related disease

Yabe, Hayato ; Kamekura, Ryuta ; Yamamoto, Motohisa ; [et al.]

Oxford University Press (OUP) ; 2021

In: Modern Rheumatology Vol. 31, No. 1 ( 2021-01-02), p. 249-260

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In: Modern Rheumatology, Oxford University Press (OUP), Vol. 31, No. 1 ( 2021-01-02), p. 249-260

Type of Medium: Online Resource

ISSN: 1439-7595 , 1439-7609

URL: Article

DOI: 10.1080/14397595.2020.1719576

Language: English

Publisher: Oxford University Press (OUP)

Publication Date: 2021

detail.hit.zdb_id: 2023498-3

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Table_8.xlsx

Murayama, Kosuke ; Ikegami, Ippei ; Kamekura, Ryuta ; [et al.]

Frontiers Media SA ; 2022

In: Frontiers in Immunology Vol. 13 ( 2022-8-25)

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In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-8-25)

Abstract: T follicular helper (Tfh) cells drive humoral immunity by facilitating B cell responses at the initial and recall phases. Recent studies have indicated the possible involvement of Tfh cells in the process of chronic inflammation. However, the functional role of Tfh cells in persistent immune settings remains unclear. Here, we report that CD4 + CD8 + (double-positive, DP; CD3 + CD4 + CD8 + CXCR5 hi PD-1 hi ) Tfh cells, a subset of germinal-center-type Tfh cells, were abundantly present in the fibroinflammatory lesions of patients with immunoglobulin G4-related disease (IgG4-RD). Transcriptome analyses showed that these DP-Tfh cells in the lesions of IgG4-RD preferentially expressed signature genes characteristic of cytotoxic CD8 + T cells, such as Eomes, CRTAM, GPR56, and granzymes, in addition to CD70. Scatter diagram analyses to examine the relationships between tissue-resident lymphocytes and various clinical parameters revealed that the levels of DP-Tfh cells were inversely correlated to the levels of serum IgG4 and local IgG4-expressing (IgG4 + ) memory B cells (CD19 + CD27 + IgD - ) in patients with IgG4-RD. Cell culture experiments using autologous tonsillar lymphocytes further suggested that DP-Tfh cells possess a poor B-cell helper function and instead regulate memory B cells. Since CD4 + (single positive, SP; CD3 + CD4 + CD8 - CXCR5 hi PD-1 hi ) Tfh cells differentiated into DP-Tfh cells under stimulation with IL-2 and IL-7 as assessed by in vitro experiments, these data imply that SP-Tfh cells are a possible origin of DP-Tfh cells under persistent inflammation. These findings highlight the potential feedback loop mechanism of Tfh cells in immune tolerance under chronic inflammatory conditions. Further studies on DP-Tfh cells may facilitate control of unresolved humoral responses in IgG4-RD pathological inflammation.

Type of Medium: Online Resource

ISSN: 1664-3224

URL: Article

DOI: 10.3389/fimmu.2022.941385

DOI: 10.3389/fimmu.2022.941385.s001

DOI: 10.3389/fimmu.2022.941385.s002

DOI: 10.3389/fimmu.2022.941385.s003

DOI: 10.3389/fimmu.2022.941385.s004

DOI: 10.3389/fimmu.2022.941385.s005

DOI: 10.3389/fimmu.2022.941385.s006

DOI: 10.3389/fimmu.2022.941385.s007

DOI: 10.3389/fimmu.2022.941385.s008

Language: Unknown

Publisher: Frontiers Media SA

Publication Date: 2022

detail.hit.zdb_id: 2606827-8

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Aberrant populations of circulating T follicular helper cells and regulatory B cells underlying idiopathic pulmonary fibrosis

Asai, Yuichiro ; Chiba, Hirofumi ; Nishikiori, Hirotaka ; [et al.]

Springer Science and Business Media LLC ; 2019

In: Respiratory Research Vol. 20, No. 1 ( 2019-12)

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In: Respiratory Research, Springer Science and Business Media LLC, Vol. 20, No. 1 ( 2019-12)

Abstract: T follicular helper (Tfh) cells have been identified as a new category of helper T cells, which express CXCR5 on their surface and induce the production of antigen-specific antibodies. Many investigations have found morbid proliferation and/or activation of Tfh cells in systemic autoimmune and allergic diseases. It is also known that Tfh cells are regulated by regulatory B (Breg) cells in the deteriorating such diseases. Recently, CXCL13, a ligand of CXCR5, has been reported to increase in the peripheral blood and lungs of patients with idiopathic pulmonary fibrosis (IPF). This study aimed to investigate the involvement of Tfh cells and Breg cells in IPF. Methods Peripheral blood samples were obtained from 18 patients with IPF. We isolated heparinized peripheral blood mononuclear cells and investigated the proportions of Breg cells, Tfh cells, PD-1 + ICOS + Tfh cells (activated form of Tfh cells), and the Tfh-cell subsets by flow cytometry. These cell profiles were compared with those of 21 healthy controls. Furthermore, we investigated the correlations between profiles of lymphocytes and lung physiology. Results The median proportions of Tfh cells per total CD4 + T cells and of PD-1 + ICOS + proportion of Tfh cells per total Tfh cells was significantly more in the IPF patients (20.4 and 5.2%, respectively) compared with healthy controls (15.4 and 2.1%, respectively; p = 0.042 and p = 0.004, respectively). The proportion of Tfh2 cells per total Tfh cells was significantly higher and the proportion of Tfh17 was smaller in the IPF patients than healthy controls. The percentage of Breg cells to total B cells was significantly decreased in the IPF patients (median, 8.5%) compared with that in the controls (median, 19.7%; p 〈 0.001). The proportion of Breg cells was positively correlated with the annual relative change in diffusing capacity of the lungs for carbon monoxide in the IPF patients ( r = 0.583, p = 0.018). Conclusion Proliferation and activation of Tfh cells and a decrease in Breg cells were observed in the peripheral blood of patients with IPF. The profile of the Tfh-cell subset also changed. Specific humoral immunity aberration would likely underlie complicated pathophysiology of IPF.

Type of Medium: Online Resource

ISSN: 1465-993X

URL: Article

DOI: 10.1186/s12931-019-1216-6

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2019

detail.hit.zdb_id: 2041675-1

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Effects of obesity on CC16 and their potential role in overweight/obese asthma

Goudarzi, Houman ; Kimura, Hirokazu ; Kimura, Hiroki ; [et al.]

Springer Science and Business Media LLC ; 2022

In: Respiratory Research Vol. 23, No. 1 ( 2022-12)

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In: Respiratory Research, Springer Science and Business Media LLC, Vol. 23, No. 1 ( 2022-12)

Abstract: Club cell secretory protein-16 (CC16) is a major anti-inflammatory protein expressed in the airway; however, the potential role of CC16 on overweight/obese asthma has not been assessed. In this study, we examined whether obesity reduces airway/circulatory CC16 levels using experimental and epidemiological studies. Then, we explored the mediatory role of CC16 in the relationship of overweight/obesity with clinical asthma measures. Methods Circulating CC16 levels were assessed by ELISA in three independent human populations, including two groups of healthy and general populations and asthma patients. The percentage of cells expressing club markers in obese vs. non-obese mice and human airways was determined by immunohistochemistry. A causal mediation analysis was conducted to determine whether circulatory CC16 acted as a mediator between overweight/obesity and clinical asthma measures. Results BMI was significantly and monotonously associated with reduced circulating CC16 levels in all populations. The percentage of CC16-expressing cells was reduced in the small airways of both mice and humans with obesity. Finally, mediation analysis revealed significant contributions of circulatory CC16 in the association between BMI and clinical asthma measures; 21.8% of its total effect in BMI’s association with airway hyperresponsiveness of healthy subjects (p = 0.09), 26.4% with asthma severity (p = 0.030), and 23% with the required dose of inhaled corticosteroid (p = 0.042). In logistic regression analysis, 1-SD decrease in serum CC16 levels of asthma patients was associated with 87% increased odds for high dose ICS requirement (p 〈 0.001). Conclusions We demonstrate that airway/circulating CC16, which is inversely associated with BMI, may mediate development and severity in overweight/obese asthma.

Type of Medium: Online Resource

ISSN: 1465-993X

URL: Article

DOI: 10.1186/s12931-022-02038-1

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2022

detail.hit.zdb_id: 2041675-1

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Distinct Phenotypes of Smokers with Fixed Airflow Limitation Identified by Cluster Analysis of Severe Asthma

Konno, Satoshi ; Taniguchi, Natsuko ; Makita, Hironi ; [et al.]

American Thoracic Society ; 2018

In: Annals of the American Thoracic Society Vol. 15, No. 1 ( 2018-01), p. 33-41

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In: Annals of the American Thoracic Society, American Thoracic Society, Vol. 15, No. 1 ( 2018-01), p. 33-41

Type of Medium: Online Resource

ISSN: 2329-6933 , 2325-6621

URL: Article

DOI: 10.1513/AnnalsATS.201701-065OC

Language: English

Publisher: American Thoracic Society

Publication Date: 2018

detail.hit.zdb_id: 2702474-X

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Increased Levels of Circulating Interleukin-18 in Patients with Advanced Tuberculosis

YAMADA, GEN ; SHIJUBO, NORIHARU ; SHIGEHARA, KATSUNORI ; [et al.]

American Thoracic Society ; 2000

In: American Journal of Respiratory and Critical Care Medicine Vol. 161, No. 6 ( 2000-06-01), p. 1786-1789

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In: American Journal of Respiratory and Critical Care Medicine, American Thoracic Society, Vol. 161, No. 6 ( 2000-06-01), p. 1786-1789

Type of Medium: Online Resource

ISSN: 1073-449X , 1535-4970

URL: Article

DOI: 10.1164/ajrccm.161.6.9911054

RVK:

XA 21200

Language: English

Publisher: American Thoracic Society

Publication Date: 2000

detail.hit.zdb_id: 1468352-0

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Increased Levels of Interleukin-18 in Patients with Pulmonary Sarcoidosis

SHIGEHARA, KATSUNORI ; SHIJUBO, NORIHARU ; OHMICHI, MITSUHIDE ; [et al.]

American Thoracic Society ; 2000

In: American Journal of Respiratory and Critical Care Medicine Vol. 162, No. 5 ( 2000-11-01), p. 1979-1982

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In: American Journal of Respiratory and Critical Care Medicine, American Thoracic Society, Vol. 162, No. 5 ( 2000-11-01), p. 1979-1982

Type of Medium: Online Resource

ISSN: 1073-449X , 1535-4970

URL: Article

DOI: 10.1164/ajrccm.162.5.9911113

RVK:

XA 21200

Language: English

Publisher: American Thoracic Society

Publication Date: 2000

detail.hit.zdb_id: 1468352-0

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Serum periostin is associated with body mass index and allergic rhinitis in healthy and asthmatic subjects

Kimura, Hirokazu ; Konno, Satoshi ; Makita, Hironi ; [et al.]

Elsevier BV ; 2018

In: Allergology International Vol. 67, No. 3 ( 2018-07), p. 357-363

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In: Allergology International, Elsevier BV, Vol. 67, No. 3 ( 2018-07), p. 357-363

Type of Medium: Online Resource

ISSN: 1323-8930

URL: Article

DOI: 10.1016/j.alit.2017.11.006

Language: English

Publisher: Elsevier BV

Publication Date: 2018

detail.hit.zdb_id: 2003098-8

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Cutting Edge: A Critical Role of Lesional T Follicular Helper Cells in the Pathogenesis of IgG4-Related Disease

Kamekura, Ryuta ; Takano, Kenichi ; Yamamoto, Motohisa ; [et al.]

The American Association of Immunologists ; 2017

In: The Journal of Immunology Vol. 199, No. 8 ( 2017-10-15), p. 2624-2629

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In: The Journal of Immunology, The American Association of Immunologists, Vol. 199, No. 8 ( 2017-10-15), p. 2624-2629

Abstract: IgG4-related disease (IgG4-RD) is a newly recognized systemic chronic fibroinflammatory disease. However, the pathogenesis of IgG4-RD remains unknown. To determine the pathophysiologic features of IgG4-RD, we examined T follicular helper (Tfh) cells in lesions and blood from patients with IgG4-RD. Patients with IgG4-related dacryoadenitis and sialadenitis (IgG4-DS) showed increased infiltration of Tfh cells highly expressing programmed death 1 and ICOS in submandibular glands. Tfh cells from IgG4-DS submandibular glands had higher expression of B cell lymphoma 6 and a greater capacity to help B cells produce IgG4 than did tonsillar Tfh cells. We also found that the percentage of programmed death 1hi circulating Tfh cells in IgG4-DS patients was higher than that in healthy volunteers and was well correlated with clinical parameters. Our findings indicate that anomalous Tfh cells in tissue lesions of IgG4-RD have features distinct from those in lymphoid counterparts or blood and potentially regulate local IgG4 production in IgG4-RD.

Type of Medium: Online Resource

ISSN: 0022-1767 , 1550-6606

URL: Article

DOI: 10.4049/jimmunol.1601507

RVK:

XA 54100

RVK:

XA 10000

Language: English

Publisher: The American Association of Immunologists

Publication Date: 2017

detail.hit.zdb_id: 1475085-5

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Applicable predictive factors extracted from peak flow trajectory for the prediction of asthma exacerbation

Yang, Yichi ; Kimura, Hirokazu ; Yokota, Isao ; [et al.]

Elsevier BV ; 2024

In: Annals of Allergy, Asthma & Immunology Vol. 132, No. 4 ( 2024-04), p. 469-476

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In: Annals of Allergy, Asthma & Immunology, Elsevier BV, Vol. 132, No. 4 ( 2024-04), p. 469-476

Type of Medium: Online Resource

ISSN: 1081-1206

URL: Article

DOI: 10.1016/j.anai.2023.11.015

Language: English

Publisher: Elsevier BV

Publication Date: 2024

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