2017年6月19日，世界著名期刊《The Journal of Allergy and Clinical Immunology》在線發表了復旦大學生物醫學研究院周玉峰課題組和約翰霍普金斯大學醫學院Peisong Gao教授合作的一篇研究論文，研究揭示了甘露糖受體調節過敏性炎癥反應的新機制--通過miR-511-3p調節巨噬細胞極化。相關研究成果題為《甘露糖受體通過miR-511-3p調節巨噬細胞極化和過敏性炎癥》 (Mannose Receptor Modulates Macrophage Polarization and Allergic Inflammation through miR-511-3p)。周玉峰研究員為第一作者，
甘露糖受體(Mannose receptor，MR)屬于C型凝集素超家族成員，可通過胞外區識別和結合特定的糖類分子，在識別病原體、遞呈抗原和保持內環境穩定中發揮作用。該研究發現甘露糖受體基因敲除可以影響巨噬細胞極化，表現為M1巨噬細胞極化增強，而M2巨噬細胞極化減弱，MR基因敲除鼠體內過敏反應增強。但甘露糖受體細胞內部分非常短，缺乏細胞內信號轉導結構，一個缺乏信號轉導功能的受體分子如何影響細胞極化，這非常難于解釋。研究者對MR基因分析后發現，MR基因第五內含子含有micrornAs(miR-511-3p), 甘露糖受體與miR-511-3p協同表達，miR-511-3p可抑制M1極化， MR通過協同表達的miR-511-3p調節巨噬細胞極化而調節過敏性炎癥。
研究發現miR-511-3p在體內外均有抗炎作用，可用于哮喘治療。同時發現過敏性哮喘病人體內miR-511-3p明顯降低，可用于哮喘診斷。該研究為哮喘，特別是難治性哮喘的診斷和治療提供了新策略和方法。
JACI:復旦大學周玉峰課題組揭示甘露糖受體調節過敏性炎癥反應的新機制
原文鏈接：
Mannose Receptor Modulates Macrophage Polarization and Allergic Inflammation through miR-511-3p
原文摘要：
BackgroundMannose receptor (MRC1/CD206) has been suggested to mediate allergic sensitization and asthma to multiple glyco-allergens, including cockroach allergens.
ObjectiveDetermine the existence of a protective mechanism through which MRC1 limits allergic inflammation through its intronic miR-511-3p.
MethodsWe examined the MRC1-mediated cockroach allergen uptake by lung macrophages and lung inflammation using C57BL/6 wild-type (WT) andMrc1-/- mice. Role of miR-511-3p in macrophage polarization and cockroach allergen-induced lung inflammation in mice transfected with Adeno-Associated Virus (AAV)-miR-511-3p (AAV-CMV-miR-511-3p-eGFP) was analyzed. Gene profiling of macrophages with or without miR-511-3p overexpression was also performed.
ResultsMrc1-/- lung macrophages showed significant reduction in cockroach allergen uptake compared with WT mice, and Mrc1-/- mice had an exacerbated lung inflammation with increased levels of cockroach allergen-specific IgE and Th2/Th17 cytokines in a cockroach allergen-induced mouse model compared to WT mice. Macrophages from Mrc1-/- mice showed significantly reduced levels of miR-511-3 and a M1 phenotype whereas over-expression of miR-511-3p rendered macrophages to exhibit a M2 phenotype. Furthermore, mice transfected with AAV-miR-511-3p showed a significant reduction in cockroach allergen-induced inflammation. Profiling of macrophages with or without miR-511-3p over-expression identified 729 differentially expressed genes, wherein the levels of Ptgds and its product PGD2 were significantly down-regulated by miR-511-3p.Ptgds showed a robust binding to miR-511-3p, which might contribute to the protective effect of miR-511-3p. The plasma levels of miR-511-3p were significantly lower in human asthmatics compared to non-asthmatic subjects.
ConclusionThese studies support a critical but previously unrecognized role of MRC1 and miR-511-3p in protection against allergen-induced lung inflammation.
