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Nasal systems immunology identifies inflammatory and tolerogenic myeloid cells that determine allergic outcome following challenge
medRxiv - Allergy and Immunology Pub Date : 2021-04-27 , DOI: 10.1101/2020.09.09.20189886
Astrid L Voskamp , Maarten L Gerdes , Roberta Menafra , Ellen Duijster , Szymon M Kielbasa , Tom Groot Kormelink , Tamar Tak , Koen A Stam , Nicolette W de Jong , Rudi W Hendricks , Susan L Kloet , Maria Yazdanbakhsh , Esther C De Jong , Roy Gerth van Wijk , Hermelijn H Smits

Innate mononuclear phagocytic system (MPS) cells preserve mucosal immune homeostasis. Here, we investigated their role at nasal mucosa following challenge with house dust mite. We combined single-cell proteome and transcriptome profiling on immune cells from nasal biopsy cells of allergic rhinitis and non-allergic subjects, before and after repeated nasal allergen challenge. Nasal biopsies of patients showed infiltrating inflammatory HLA-DRhi CD14+ monocytes and CD16+ monocytes, and transcriptional changes in resident CD1C+ CD1A+ conventional dendritic cells (cDC)2 following challenge. Importantly, although clinically silent, non-allergic individuals displayed a distinct innate MPS response to allergen challenge: predominant infiltration of myeloid-derived suppressor cells (HLA-DRlow CD14+ monocytes), as well as cDC2 clusters expressing increased inhibitory/tolerogenic transcripts. Therefore, we identified not only clusters involved in airway inflammation but also a non-inflammatory, homeostatic blueprint of innate MPS responses to allergens in non-allergic individuals. Future therapies should target innate MPS for treatment of inflammatory airway diseases.

中文翻译:

鼻系统免疫学鉴定炎症和耐受性髓样细胞,这些细胞决定攻击后的过敏结果

先天性单核吞噬系统(MPS)细胞可保持粘膜免疫稳态。在这里,我们调查了屋尘螨对它们在鼻黏膜中的作用。在反复的鼻过敏原攻击之前和之后,我们结合了单细胞蛋白质组学和转录组谱对来自过敏性鼻炎和非过敏性受试者的鼻活检细胞的免疫细胞的分析。患者的鼻活检显示浸润性炎症性HLA-DRhi CD14 +单核细胞和CD16 +单核细胞,攻击后常驻CD1C + CD1A +传统树突状细胞(cDC)2发生转录变化。重要的是,尽管临床上沉默,但非过敏性个体对过敏原挑战表现出独特的先天MPS反应:髓样来源的抑制性细胞(HLA-DRlow CD14 +单核细胞)主要浸润,以及表达增加的抑制性/致耐受性转录本的cDC2簇。因此,我们不仅确定了与气道炎症有关的簇,而且还确定了非变应性个体对变应原的先天MPS反应的非炎症,体内平衡蓝图。未来的治疗应针对先天性MPS,以治疗炎症性气道疾病。
更新日期:2021-04-28
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