原標(biāo)題：
　　IgG4驅(qū)動M2a巨噬細(xì)胞形成調(diào)控型的m2b表型-在免疫耐受中的潛在意義
　　背景：巨噬細(xì)胞在體外可以在免疫復(fù)合物(ICs)的存在下轉(zhuǎn)化為免疫調(diào)節(jié)的M2b巨噬細(xì)胞，但特異性的IgG1或IgG4亞型在這種表型和功能改變中的作用尚不清楚。
　　方法：用M-CSF處理單核細(xì)胞來源的巨噬細(xì)胞(MDMs)，然后用IL-4/IL-13誘導(dǎo)M2a過敏表型。為了模擬非特異性或特異性ICs，用骨髓瘤IgG1、IgG4或者花粉Phl p 5包被，其次是重組人Phl p 5特異性IgG1或IgG4。然后加入M2a極化巨噬細(xì)胞，通過流式細(xì)胞術(shù)、ELISA和rtPCR檢測細(xì)胞標(biāo)志物和細(xì)胞因子。此外，IgG1或IgG4形成免疫復(fù)合物使用蛋白L。
　　結(jié)果：IgG4 ICs下調(diào)M2a細(xì)胞CD163、CD206、IL-10、IL-6、TNF、CCL1分泌明顯增加，提示向M2b表型轉(zhuǎn)變。與經(jīng)IgG1處理的細(xì)胞(p=0.0335)和未經(jīng)處理的細(xì)胞(p < 0.00001)相比，用IgG4 ICs處理可導(dǎo)致FcRII表達(dá)和FcRII下調(diào)(p < 0.00001)。
　　結(jié)論：與IgG1和IgG4亞型的免疫復(fù)合物可以通過平板吸收在體外生成，而在液體形式中，IgG4亞型的FcRIIb蛋白l交聯(lián)可將原過敏的M2a巨噬細(xì)胞重定向到M2b的免疫抑制表型。這表明巨噬細(xì)胞與IgG4在免疫耐受中的相互作用，可能與過敏原免疫治療有關(guān)。


延伸閱讀
Allergy
IgG4 drives M2a macrophages to a regulatory M2b-like phenotype: potential implication in
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
　　創(chuàng)建過敏性疾病的科研、科普知識交流平臺，為過敏患者提供專業(yè)診斷、治療、預(yù)防的共享平臺。