Anti-IL-22 Antibody Attenuates Acute Graft-versus-Host Disease via Increasing Foxp3(+) T Cell through Modulation of CD11b(+) Cell Function.

Anti-IL-22 Antibody Attenuates Acute Graft-versus-Host Disease via Increasing Foxp3(+) T Cell through Modulation of CD11b(+) Cell Function.
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抗 IL-22 抗体通过调节 CD11b 细胞功能增加 Foxp3 T 细胞,从而减轻急性移植物抗宿主病

DOI:
10.1155/2018/1605341
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发表时间:
2018
影响因子:
4.1
通讯作者:
Wang X
Wang X
中科院分区:
医学3区
文献类型:
--
作者:
Wu J;Gu J;Zhou S;Lu H;Lu Y;Lu L;Wang X

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将从B6小鼠分离的脾细胞转移到正常B6 D2 F1小鼠中诱导急性移植物抗宿主病(aGVHD),导致消除受体B细胞的供体细胞毒性T淋巴细胞扩增。由Th 1细胞、Th 17细胞和先天性免疫细胞分泌的细胞因子IL-22在结构上与IL-10相关。为了研究IL-22与aGVHD之间的关联,使用抗小鼠IL-22抗体(IL-22 Ab)来消除小鼠aGVHD模型中的IL-22活性。IL-22 Ab的施用显著降低了B6移植物的B6 D2 F1受体中aGVHD的进展。IL-22 Ab处理还降低了干扰素-γ +和肿瘤坏死因子-α + T细胞的百分比,但增加了叉头框p3+调节性T细胞(TcR)的数量。在TCF 4和供体CD 11b+细胞存在下,IL-22 Ab保护免于aGVHD。当CD 4 + CD 25 − T细胞在从IL-22 Ab处理的GVHD小鼠获得的CD 11b+细胞存在下分化时,与共培养的未处理的对照细胞相比,体外Treg诱导更有效。最后,IL-22 Ab调节aGVHD小鼠中CD 11b+细胞中细胞因子和共刺激分子的表达。因此,我们得出结论,IL-22 Ab给药代表了治疗aGVHD的可行方法。
Transfer of splenocytes isolated from B6 mice into normal B6D2F1 mice induces acute graft-versus-host disease (aGVHD), resulting in the expansion of donor cytotoxic T lymphocytes that eliminate recipient B cells. The cytokine IL-22, secreted by Th1 cells, Th17 cells, and innate immune cells, is structurally related to IL-10. To investigate the association between IL-22 and aGVHD, an anti-mouse IL-22 antibody (IL-22Ab) was used to ablate IL-22 activity in a mouse aGVHD model. Administration of IL-22Ab significantly reduced the progression of aGVHD in B6D2F1 recipients of B6 grafts. IL-22Ab treatment also decreased the percentage of interferon-γ + and tumor necrosis factor-α + T cells but increased the number of forkhead box p3+ regulatory T cells (Tregs). In the presence of Tregs and donor CD11b+ cells, IL-22Ab protected against aGVHD. In vitro Treg induction was more efficient when CD4+CD25− T cells differentiated in the presence of CD11b+ cells obtained from IL-22Ab-treated GVHD mice, compared with cocultured untreated control cells. Finally, IL-22Ab modulated the expression of cytokines and costimulatory molecules in CD11b+ cells in aGVHD mice. We therefore conclude that IL-22Ab administration represents a viable approach for treating aGVHD.
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