IgG4 drives M2a macrophages to a regulatory M2b-like phenotype: potential implication in immune tolerance.
IgG4 drives M2a macrophages to a regulatory M2b-like phenotype: potential implication in immune tolerance.
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IgG4将M2A巨噬细胞驱动到调节性M2B样表型：对免疫耐受性的潜在影响。
DOI：
10.1111/all.13635
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发表时间：
2019-03
期刊：
影响因子：
12.4
通讯作者：
Jensen-Jarolim E
中科院分区：
文献类型：
--
作者：
Bianchini R;Roth-Walter F;Ohradanova-Repic A;Flicker S;Hufnagl K;Fischer MB;Stockinger H;Jensen-Jarolim E
巨噬细胞可以在免疫复合物（IC）的存在下在体外转化为免疫调节M2 b巨噬细胞，但特定亚类IgG 1或IgG 4在这种表型和功能变化中的作用尚不清楚。我们的目的是通过应用由两种独立方法构建的IgG 4或IgG 1亚类的精确定义的IC来改进原始方法。用M-CSF处理单核细胞衍生的巨噬细胞（MDM），然后用IL-4/IL-13诱导M2 a过敏表型。为了模拟非特异性或过敏原特异性IC，将板用骨髓瘤IgG 1或IgG 4包被，或用草花粉过敏原Phl p 5包被，然后用重组人Phl p 5特异性IgG 1或IgG 4包被。然后加入M2 a极化的巨噬细胞，培养，并通过流式细胞术、ELISA和rtPCR检查细胞标志物和细胞因子。或者，使用蛋白L形成具有IgG 1或IgG 4的免疫复合物。IgG 4 IC下调M2 a细胞上的CD 163和CD 206，并显著增加IL-10、IL-6、TNFα和CCL 1分泌，表明向M2 b样表型转变。与IgG 1处理的细胞（P = 0.0335）或未处理的细胞（P < 0.00001）相比，IgG 4 IC处理导致Fc γ RII的表达和FcγRII的下调。具有亚类IgG 1和IgG 4的免疫复合物可以通过平板吸收在体外产生，并且通过蛋白L以流体形式产生。通过IgG 4亚类交联FcγRIIb将促过敏性M2 a巨噬细胞重定向为M2 b样免疫抑制表型。这表明巨噬细胞与IgG 4在免疫耐受中的相互作用，可能与过敏原免疫治疗相关。
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. We aimed to refine the original method by applying precisely defined ICs of the subclasses IgG4 or IgG1 constructed by two independent 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. IgG4 ICs down regulated CD163 and CD206 on M2a cells, and significantly increased IL‐10, IL‐6, TNFα, and CCL1 secretion, indicating a shift to an M2b‐like phenotype. Treatment with IgG4 ICs resulted in expression of FcγRII and down modulation of FcγRII compared with IgG1 treated cells (P = 0.0335) or untreated cells (P < 0.00001). Immune complexes with subclasses IgG1 and IgG4 can in vitro be generated by plate absorption, and in fluid form by protein L. Cross‐linking of FcγRIIb by the IgG4 subclass redirects pro‐allergic M2a macrophages to an M2b‐like immunosuppressive phenotype. This suggests an interplay of macrophages with IgG4 in immune tolerance, likely relevant in allergen immunotherapy.
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影响因子：
5.5
作者：
Asai, Akira;Nakamura, Kiwamu;Suzuki, Fujio
通讯作者：
Suzuki, Fujio
影响因子：
4.4
作者：
Genovese, A;Borgia, G;Marone, G
通讯作者：
Marone, G
影响因子：
4.4
作者：
Fujita H;Soyka MB;Akdis M;Akdis CA
通讯作者：
Akdis CA
过敏原特异性免疫疗法的机制和对过敏原的免疫耐受性。
DOI：
10.1186/s40413-015-0063-2
发表时间：
2015
期刊：
The World Allergy Organization journal
影响因子：
--
作者：
Akdis CA;Akdis M
通讯作者：
Akdis M
DOI：
10.1073/pnas.1621280114
发表时间：
2017-06-06
影响因子：
11.1
作者：
Barsheshet, Yiftah;Wildbaum, Gizi;Karin, Nathan
通讯作者：
Karin, Nathan