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首页> 外文期刊>Clinical and experimental allergy : >Therapeutic administration of bone marrow‐derived mesenchymal stromal cells reduces airway inflammation without up‐regulating Tregs in experimental asthma
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Therapeutic administration of bone marrow‐derived mesenchymal stromal cells reduces airway inflammation without up‐regulating Tregs in experimental asthma

机译：骨髓衍生的间充质细胞的治疗施用减少了在实验性哮喘中没有上调的Tregs的呼吸道炎症

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Summary Background Prophylactic administration of mesenchymal stromal cells ( MSC s) derived from adipose ( AD ‐ MSC ) and bone marrow tissue ( BM ‐ MSC ) in ovalbumin‐induced asthma hinders inflammation in a Treg‐dependent manner. It is uncertain whether MSC s act through Tregs when inflammation is already established in asthma induced by a clinically relevant allergen. Objective Evaluate the effect of therapeutic administration of MSC s on inflammation and Treg cells in house dust mite ( HDM )‐induced asthma. Methods BM ‐ MSC s and AD ‐ MSC s were administered intratracheally to C57 BL /6 mice 1 day after the last HDM challenge. Lung function, remodelling and parenchymal inflammation were assayed 3 or 7 days after MSC s treatment, through invasive plethysmography and histology, respectively. Bronchoalveolar lavage fluid ( BALF ) and mediastinal lymph nodes ( mLN s) were assessed regarding the inflammatory profile by flow cytometry, ELISA and qRT‐PCR. MSC s were studied regarding their potential to induce Treg cells from primed and unprimed lymphocytes in vitro. Results BM ‐ MSC s, but not AD ‐ MSC s, reduced lung influx of eosinophils and B cells and increased IL ‐10 levels in HDM ‐challenged mice. Neither BM ‐ MSC s nor AD ‐ MSC s reduced lung parenchymal inflammation, airway hyperresponsiveness or mucus hypersecretion. BM ‐ MSC s and AD ‐ MSC s did not up‐regulate Treg cell counts within the airways and mLN s, but BM ‐ MSC s decreased the pro‐inflammatory profile of alveolar macrophages. Co‐culture of BM ‐ MSC s and AD ‐ MSC s with allergen‐stimulated lymphocytes reduced Treg cell counts in a cell‐to‐cell contact‐independent manner, although co‐culture of both MSC s with unprimed lymphocytes up‐regulated Treg cell counts. Conclusions MSC s therapeutically administered exert anti‐inflammatory effects in the airway of HDM ‐challenged mice, but do not ameliorate lung function or remodelling. Although MSC pre‐treatment can increase Treg cell numbers, it is highly unlikely that the MSC s will induce Treg cell expansion when lymphocytes are allergenically primed in an established lung inflammation.
机译：发明内容卵形蛋白诱导的哮喘诱导的哮喘诱导的哮喘抑制症中衍生自脂肪（Ad - MSC）和骨髓组织（BM-MSC）的间充质基质细胞（MSC S）的预防施用施用以Treg依赖性方式。当临床相关过敏原诱导的哮喘已经建立炎症时，不确定MSC S是否通过Tregs作用。目的评价治疗施用MSCS对房屋粉尘（HDM）诱导的哮喘内炎症和Treg细胞的影响。方法BM-MSC S和AD - MSC S在最后一次HDM挑战后1天内给予C57 BL / 6小鼠。通过侵入性体检和组织学分别在MSC治疗后3或7天测定肺功能，重塑和实体炎症。通过流式细胞术，ELISA和QRT-PCR评估炎症性的支气管肺泡灌洗液（BALF）和纵隔淋巴结（MLN S）。研究了MSC S，其有可能在体外诱导来自灌注和未预先的淋巴细胞的Treg细胞。结果BM - MSC S，但不是AD - MSC S，降低嗜酸性粒细胞和B细胞的肺部流量，并增加了HDM挑战小鼠的IL -10水平。 BM - MSC S也不是AD - MSC的肺实质炎症，气道高反应性或粘液过度折杂。 BM - MSC S和AD - MSC S没有上调气道和MLN S内的Treg细胞计数，但BM-MSC S降低了肺泡巨噬细胞的促炎症曲线。 BM - MSC S和AD - MSC S的共培养，具有过敏原刺激的淋巴细胞减少了Treg细胞计数的细胞 - 细胞接触独立的方式，尽管MSC S的共同培养有未预先淋巴细胞上调的Treg细胞计数。结论MSC S治疗施用在HDM挑战小鼠气道中的抗炎作用，但不改善肺功能或重塑。虽然MSC预处理可以增加Treg细胞数，但是，当淋巴细胞在已建立的肺炎中过敏灌注时，MSC S会诱导Treg细胞扩张。

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    Kitoko J. Z.; de Castro L. L.; Nascimento A. P.; Abreu S. C.; Cruz F. F.; Arantes A. C.; Xisto D. G.; Martins M. A.; Morales M. M.; Rocco P. R. M.; Olsen P. C.;

  • 作者单位

    Laboratory of Clinical Bacteriology and ImmunologyFederal University of Rio de JaneiroRio de;

    Laboratory of Pulmonary InvestigationFederal University of Rio de JaneiroRio de Janeiro Brazil;

    Laboratory of Clinical Bacteriology and ImmunologyFederal University of Rio de JaneiroRio de;

    Laboratory of Pulmonary InvestigationFederal University of Rio de JaneiroRio de Janeiro Brazil;

    Laboratory of Pulmonary InvestigationFederal University of Rio de JaneiroRio de Janeiro Brazil;

    Laboratory of InflammationOswaldo Cruz FoundationRio de Janeiro Brazil;

    Laboratory of Pulmonary InvestigationFederal University of Rio de JaneiroRio de Janeiro Brazil;

    Laboratory of InflammationOswaldo Cruz FoundationRio de Janeiro Brazil;

    Laboratory of Cellular and Molecular PhysiologyFederal University of Rio de JaneiroRio de Janeiro;

    Laboratory of Pulmonary InvestigationFederal University of Rio de JaneiroRio de Janeiro Brazil;

    Laboratory of Clinical Bacteriology and ImmunologyFederal University of Rio de JaneiroRio de;

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  • 正文语种 eng
  • 中图分类 医学免疫学;
  • 关键词

    airway inflammation; asthma; mesenchymal stromal cells; Treg;

    机译：气道炎症;哮喘;间充质基质细胞;Treg;

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