原標(biāo)題：巨噬細(xì)胞源性的顆粒蛋白前體促進(jìn)過(guò)敏原誘導(dǎo)的氣道炎癥
背景：顆粒前體蛋白（Progranulin，PGRN）主要由免疫細(xì)胞和上皮細(xì)胞產(chǎn)生，參與多種炎癥性疾病的發(fā)生發(fā)展。然而，PGRN在過(guò)敏性氣道炎癥中的作用尚不清楚，本研究主要研究了PGRN在過(guò)敏性氣道炎癥中的作用。
方法：對(duì)屋塵螨過(guò)敏原致敏小鼠氣道PGRN和2型細(xì)胞因子的產(chǎn)生進(jìn)行了檢測(cè)，并用巨噬細(xì)胞、氣道上皮細(xì)胞和NKT細(xì)胞系研究這些分子的主要細(xì)胞來(lái)源。通過(guò)評(píng)估支氣管肺泡灌洗液中細(xì)胞因子水平和組織病理學(xué)，闡明PGRN在巨噬細(xì)胞源性PGRN缺乏小鼠和NKT細(xì)胞敲除小鼠哮喘模型過(guò)敏性氣道炎癥中的作用。本研究還在小鼠模型中加入了重組PGRN，以確認(rèn)PGRN在過(guò)敏性氣道炎癥中的作用。
結(jié)果：在暴露于過(guò)敏原的氣道中，PGRN的產(chǎn)生先于其他細(xì)胞因子，主要來(lái)自巨噬細(xì)胞。PGRN誘導(dǎo)NKT細(xì)胞中IL-4和IL-13的產(chǎn)生以及氣道上皮細(xì)胞中IL-33和TSLP的產(chǎn)生。在NKT缺陷小鼠中，PGRN誘導(dǎo)的Th2細(xì)胞因子產(chǎn)生被抑制。最后，在暴露于過(guò)敏原的PGRN缺乏的小鼠中，過(guò)敏性炎癥顯著減弱，但是在致敏期間加入重組PGRN后炎癥恢復(fù)。
結(jié)論：在致敏早期，氣道中巨噬細(xì)胞源性PGRN的存在可能對(duì)于啟動(dòng)Th2免疫反應(yīng)以及通過(guò)誘導(dǎo)NKT和氣道上皮細(xì)胞中2型細(xì)胞因子的產(chǎn)生引起過(guò)敏性氣道炎癥途徑至關(guān)重要。


延伸閱讀
Allergy                                                
Early pubertal maturation and risk of childhood asthma: A mendelian randomization and longitudinal study
DOI: 10.1111/all.14009
Abstract:
Background: Progranulin (PGRN), mainly produced by immune and epithelial cells, has been known to be involved in the development of various inflammatory diseases. However, the function of PGRN in allergic airway inflammation has not been clearly elucidated, we investigated the role of PGRN in allergic airway inflammation.
Methods: Production of PGRN and various type 2 cytokines were evaluated in mouse airways exposed to house dust mite allergen and main cellular sources of these molecules were investigated using in macrophage, airway epithelial cell, and NKT cell lines. We elucidated the role of PGRN in allergic airway inflammation in mouse models of asthma using macrophage derived PGRN-deficient mice and NKT cell knock out mice by evaluating cytokine levels in bronchoalveolar lavage fluids and histopathology. We also supplemented recombinant PGRN in the mouse models to confirm the role of PGRN in allergic airway inflammation.
Results: PGRN production preceded other cytokines, mainly from macrophages, in the airway exposed to allergen. PGRN induced IL-4 and IL-13 production in NKT cells and IL-33 and TSLP in airway epithelial cells. PGRN induced Th2 cytokine production was abolished in NKT-deficient mice. Finally, allergic inflammation was significantly attenuated in allergen-exposed PGRNdeficient mice, but inflammation was restored when recombinant PGRN was supplemented during the allergen sensitization period.
Conclusion: The presence of macrophage-derived PGRN in airways in the early sensitization period may be critical for mounting a Th2 immune response and for following an allergic airway inflammation pathway via induction of type 2 cytokine production in NKT and airway epithelial cells.
First Author:
Jun-Pyo Choi  
Correspondence:
Division of Allergy and Clinical Immunology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Republic of Korea
All Authors:
Jun-Pyo Choi, So Young Park, Keun-Ai Moon, Eun Hee Ha, Yeon Duk Woo, Doo Hyun Chung, Hyouk-Soo Kwon, Tae-Bum Kim, Hae-Sim Park, Hee-Bom Moon, Woo-Jung Song and You Sook Cho
　　創(chuàng)建過(guò)敏性疾病的科研、科普知識(shí)交流平臺(tái)，為過(guò)敏患者提供專業(yè)診斷、治療、預(yù)防的共享平臺(tái)。