杭州浙大迪迅生物基因工程有限公司Allergy：IgG4驱动M2a巨噬细胞形成调控型的m2b表型
发布日期：2019-07-31
原标题：
IgG4驱动M2a巨噬细胞形成调控型的m2b表型-在免疫耐受中的潜在意义
方法：用M-CSF处理单核细胞来源的巨噬细胞(MDMs)，然后用IL-4/IL-13诱导M2a过敏表型。为了模拟非特异性或特异性ICs，用骨髓瘤IgG1、IgG4或者花粉Phl p 5包被，其次是重组人Phl p 5特异性IgG1或IgG4。然后加入M2a极化巨噬细胞，通过流式细胞术、ELISA和rtPCR检测细胞标志物和细胞因子。此外，IgG1或IgG4形成免疫复合物使用蛋白L。
结果：IgG4 ICs下调M2a细胞CD163、CD206、IL-10、IL-6、TNF、CCL1分泌明显增加，提示向M2b表型转变。与经IgG1处理的细胞(p=0.0335)和未经处理的细胞(p < 0.00001)相比，用IgG4 ICs处理可导致FcRII表达和FcRII下调(p < 0.00001)。
结论：与IgG1和IgG4亚型的免疫复合物可以通过平板吸收在体外生成，而在液体形式中，IgG4亚型的FcRIIb蛋白l交联可将原过敏的M2a巨噬细胞重定向到M2b的免疫抑制表型。这表明巨噬细胞与IgG4在免疫耐受中的相互作用，可能与过敏原免疫治疗有关。
延伸阅读
Allergy
immune tolerance
DOI: 10.1111/all.13635
Abstract:
Background: Macrophages can be converted in vitro into immunoregulatory M2b macrophages in the presence of immune complexes (ICs), but the role of the specific subclasses IgG1 or IgG4 in this phenotypic and functional change is not known.
Methods: Monocyte-derived macrophages (MDMs) were treated with M-CSF, followed by IL-4/IL-13 to induce the M2a allergic phenotype. To mimic unspecific or allergen-specific ICs, plates were coated with myeloma IgG1 or IgG4, or with grass pollen allergen Phl p 5 followed by recombinant human Phl p 5-specific IgG1 or IgG4. M2a polarized macrophages were then added, cultured and examined for cellular markers and cytokines by flow cytometry, ELISA, and rtPCR. Alternatively, immune complexes with IgG1 or IgG4 were formed using protein L.
Results: IgG4 ICs down-regulated CD163 and CD206 on M2a cells, and significantly increased IL-10, IL-6, TNF and CCL1 secretion, indicating a shift to an M2b-like phenotype. Treatment with IgG4 ICs resulted in expression of FcgRII and down-modulation of FcgRII compared to IgG1 treated cells (p=0.0335) or untreated cells (p < 0.00001).
Conclusion: Immune complexes with subclasses IgG1 and IgG4 can in vitro be generated by plate
absorption, and in fluid form by protein L. Crosslinking of FcgRIIb by the IgG4 subclass redirects proallergic M2a macrophages to an M2b-like immunosuppressive phenotype. This suggests an interplay of macrophages with IgG4 in immune tolerance, likely relevant in allergen immunotherapy.
First Author:
Rodolfo Bianchini
Correspondence:
The Interuniversity Messerli Research Institute, University of Veterinary Medicine Vienna, Medical University of Vienna, Dept. of Comparative Medicine (Vienna,Austria)
All Authors:
Rodolfo Bianchini, Franziska Roth-Walter, Anna Ohradanova-Repic, Sabine Flicker, Karin Hufnagl,Michael Bernhard Fischer, Hannes Stockinger ,Erika Jensen-Jarolim
IgG4驱动M2a巨噬细胞形成调控型的m2b表型-在免疫耐受中的潜在意义
——浙大迪迅 译
背景：巨噬细胞在体外可以在免疫复合物(ICs)的存在下转化为免疫调节的M2b巨噬细胞，但特异性的IgG1或IgG4亚型在这种表型和功能改变中的作用尚不清楚。方法：用M-CSF处理单核细胞来源的巨噬细胞(MDMs)，然后用IL-4/IL-13诱导M2a过敏表型。为了模拟非特异性或特异性ICs，用骨髓瘤IgG1、IgG4或者花粉Phl p 5包被，其次是重组人Phl p 5特异性IgG1或IgG4。然后加入M2a极化巨噬细胞，通过流式细胞术、ELISA和rtPCR检测细胞标志物和细胞因子。此外，IgG1或IgG4形成免疫复合物使用蛋白L。
结果：IgG4 ICs下调M2a细胞CD163、CD206、IL-10、IL-6、TNF、CCL1分泌明显增加，提示向M2b表型转变。与经IgG1处理的细胞(p=0.0335)和未经处理的细胞(p < 0.00001)相比，用IgG4 ICs处理可导致FcRII表达和FcRII下调(p < 0.00001)。
结论：与IgG1和IgG4亚型的免疫复合物可以通过平板吸收在体外生成，而在液体形式中，IgG4亚型的FcRIIb蛋白l交联可将原过敏的M2a巨噬细胞重定向到M2b的免疫抑制表型。这表明巨噬细胞与IgG4在免疫耐受中的相互作用，可能与过敏原免疫治疗有关。
延伸阅读
Allergy
[IF:6.048]
IgG4 drives M2a macrophages to a regulatory M2b-like phenotype: potential implication inimmune tolerance
DOI: 10.1111/all.13635
Abstract:
Background: Macrophages can be converted in vitro into immunoregulatory M2b macrophages in the presence of immune complexes (ICs), but the role of the specific subclasses IgG1 or IgG4 in this phenotypic and functional change is not known.
Methods: Monocyte-derived macrophages (MDMs) were treated with M-CSF, followed by IL-4/IL-13 to induce the M2a allergic phenotype. To mimic unspecific or allergen-specific ICs, plates were coated with myeloma IgG1 or IgG4, or with grass pollen allergen Phl p 5 followed by recombinant human Phl p 5-specific IgG1 or IgG4. M2a polarized macrophages were then added, cultured and examined for cellular markers and cytokines by flow cytometry, ELISA, and rtPCR. Alternatively, immune complexes with IgG1 or IgG4 were formed using protein L.
Results: IgG4 ICs down-regulated CD163 and CD206 on M2a cells, and significantly increased IL-10, IL-6, TNF and CCL1 secretion, indicating a shift to an M2b-like phenotype. Treatment with IgG4 ICs resulted in expression of FcgRII and down-modulation of FcgRII compared to IgG1 treated cells (p=0.0335) or untreated cells (p < 0.00001).
Conclusion: Immune complexes with subclasses IgG1 and IgG4 can in vitro be generated by plate
absorption, and in fluid form by protein L. Crosslinking of FcgRIIb by the IgG4 subclass redirects proallergic M2a macrophages to an M2b-like immunosuppressive phenotype. This suggests an interplay of macrophages with IgG4 in immune tolerance, likely relevant in allergen immunotherapy.
First Author:
Rodolfo Bianchini
Correspondence:
The Interuniversity Messerli Research Institute, University of Veterinary Medicine Vienna, Medical University of Vienna, Dept. of Comparative Medicine (Vienna,Austria)
All Authors:
Rodolfo Bianchini, Franziska Roth-Walter, Anna Ohradanova-Repic, Sabine Flicker, Karin Hufnagl,Michael Bernhard Fischer, Hannes Stockinger ,Erika Jensen-Jarolim
2019-06-27 Article
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