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邻苯二甲酸二丁酯诱导的胸腺基质淋巴细胞生成素是 Th2 接触性超敏反应所必需的。

Dibutyl phthalate-induced thymic stromal lymphopoietin is required for Th2 contact hypersensitivity responses.

机构信息

Department of Immunology, University of Washington, Seattle, WA 98195, USA.

出版信息

J Immunol. 2010 Mar 15;184(6):2974-84. doi: 10.4049/jimmunol.0803478. Epub 2010 Feb 19.


DOI:10.4049/jimmunol.0803478
PMID:20173025
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2922850/
Abstract

Thymic stromal lymphopoietin (TSLP) is an IL-7-related cytokine, produced by epithelial cells, that has been linked to atopic dermatitis and asthma; however, it remains unclear how TSLP shapes the adaptive immune response that causes these allergic disorders. In this study, we demonstrate a role for TSLP in a Th2 model of contact hypersensitivity in mice. TSLP is required for the development of Th2-type contact hypersensitivity induced by the hapten FITC in combination with the sensitizing agent dibutyl phthalate. TSLPR-deficient mice exhibited a dramatically reduced response, including markedly reduced local infiltration by eosinophils, Th2 cytokine production, and serum IgE levels, following FITC sensitization and challenge. The reduced response by TSLPR-deficient mice is likely due to decreased frequency and reduced T cell stimulatory function of skin-derived Ag-bearing FITC(+)CD11c(+) dendritic cells in draining lymph nodes following FITC sensitization. These data suggest that skin-derived dendritic cells are direct or indirect targets of TSLP in the development of type 2 immune responses in the skin, where TSLP drives their maturation, accumulation in skin draining lymph nodes, and ability to induce proliferation of naive allergen-specific T cells.

摘要

胸腺基质淋巴细胞生成素 (TSLP) 是一种与白细胞介素 7 相关的细胞因子,由上皮细胞产生,与特应性皮炎和哮喘有关;然而,TSLP 如何塑造导致这些过敏疾病的适应性免疫反应仍不清楚。在这项研究中,我们证明了 TSLP 在小鼠接触性超敏反应的 Th2 模型中的作用。在与敏化剂邻苯二甲酸二丁酯联合使用半抗原 FITC 诱导的 Th2 型接触性超敏反应中,TSLP 是必需的。TSLPR 缺陷小鼠表现出明显的反应降低,包括 FITC 敏化和挑战后局部嗜酸性粒细胞浸润、Th2 细胞因子产生和血清 IgE 水平明显降低。TSLPR 缺陷小鼠的反应降低可能是由于 FITC 敏化后引流淋巴结中皮肤来源的 Ag 结合 FITC(+)CD11c(+)树突状细胞的频率降低和 T 细胞刺激功能降低。这些数据表明,皮肤来源的树突状细胞是 TSLP 在皮肤中诱导 2 型免疫反应中的直接或间接靶标,TSLP 驱动其成熟、在皮肤引流淋巴结中的积累以及诱导幼稚过敏原特异性 T 细胞增殖的能力。

相似文献

[1]
Dibutyl phthalate-induced thymic stromal lymphopoietin is required for Th2 contact hypersensitivity responses.

J Immunol. 2010-2-19

[2]
Phthalate ester-induced thymic stromal lymphopoietin mediates allergic dermatitis in mice.

Immunology. 2009-3-23

[3]
TSLP acts on infiltrating effector T cells to drive allergic skin inflammation.

Proc Natl Acad Sci U S A. 2008-8-19

[4]
Cutting edge: identification of the thymic stromal lymphopoietin-responsive dendritic cell subset critical for initiation of type 2 contact hypersensitivity.

J Immunol. 2013-10-11

[5]
Langerhans cells are critical in epicutaneous sensitization with protein antigen via thymic stromal lymphopoietin receptor signaling.

J Allergy Clin Immunol. 2012-3-3

[6]
Thymic stromal lymphopoietin-activated plasmacytoid dendritic cells induce the generation of FOXP3+ regulatory T cells in human thymus.

J Immunol. 2010-2-19

[7]
Intradermal administration of thymic stromal lymphopoietin induces a T cell- and eosinophil-dependent systemic Th2 inflammatory response.

J Immunol. 2008-9-15

[8]
Early production of thymic stromal lymphopoietin precedes infiltration of dendritic cells expressing its receptor in allergen-induced late phase cutaneous responses in atopic subjects.

Allergy. 2009-7

[9]
Antagonistic effect of the inflammasome on thymic stromal lymphopoietin expression in the skin.

J Allergy Clin Immunol. 2013-8-13

[10]
Thymic stromal lymphopoietin interferes with airway tolerance by suppressing the generation of antigen-specific regulatory T cells.

J Immunol. 2011-2-15

引用本文的文献

[1]
Distinct roles for thymic stromal lymphopoietin (TSLP) and IL-33 in experimental eosinophilic esophagitis.

bioRxiv. 2025-3-1

[2]
Site-specific regulation of Th2 differentiation within lymph node microenvironments.

J Exp Med. 2024-4-1

[3]
Neuroimmune interactions in atopic and allergic contact dermatitis.

J Allergy Clin Immunol. 2023-5

[4]
7-Methoxyisoflavone ameliorates atopic dermatitis symptoms by regulating multiple signaling pathways and reducing chemokine production.

Sci Rep. 2022-5-24

[5]
Alarmin Cytokines as Central Regulators of Cutaneous Immunity.

Front Immunol. 2022

[6]
Information flow in the spatiotemporal organization of immune responses.

Immunol Rev. 2022-3

[7]
Contact dermatitis.

Nat Rev Dis Primers. 2021-5-27

[8]
Associations among phthalate exposure, DNA methylation of TSLP, and childhood allergy.

Clin Epigenetics. 2021-4-9

[9]
Keratinocytes control skin immune homeostasis through de novo-synthesized glucocorticoids.

Sci Adv. 2021-1-29

[10]
The Gastrointestinal Helminth Suppresses Inflammation in a Model of Contact Hypersensitivity.

Front Immunol. 2020

本文引用的文献

[1]
Basophils contribute to T(H)2-IgE responses in vivo via IL-4 production and presentation of peptide-MHC class II complexes to CD4+ T cells.

Nat Immunol. 2009-7

[2]
Basophils function as antigen-presenting cells for an allergen-induced T helper type 2 response.

Nat Immunol. 2009-7

[3]
MHC class II-dependent basophil-CD4+ T cell interactions promote T(H)2 cytokine-dependent immunity.

Nat Immunol. 2009-7

[4]
A homozygous frameshift mutation in the mouse Flg gene facilitates enhanced percutaneous allergen priming.

Nat Genet. 2009-5

[5]
TSLP regulates intestinal immunity and inflammation in mouse models of helminth infection and colitis.

J Exp Med. 2009-3-16

[6]
TSLP conditions the lung immune environment for the generation of pathogenic innate and antigen-specific adaptive immune responses.

J Immunol. 2009-2-1

[7]
A small molecule CRTH2 antagonist inhibits FITC-induced allergic cutaneous inflammation.

Int Immunol. 2009-1

[8]
Reversal of thymic stromal lymphopoietin-induced airway inflammation through inhibition of Th2 responses.

J Immunol. 2008-11-1

[9]
Intradermal administration of thymic stromal lymphopoietin induces a T cell- and eosinophil-dependent systemic Th2 inflammatory response.

J Immunol. 2008-9-15

[10]
TSLP acts on infiltrating effector T cells to drive allergic skin inflammation.

Proc Natl Acad Sci U S A. 2008-8-19

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