An FcRn-dependent role for anti-flagellin immunoglobulin G in pathogenesis of colitis in mice.
An FcRn-dependent role for anti-flagellin immunoglobulin G in pathogenesis of colitis in mice.
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DOI：
10.1053/j.gastro.2009.07.059
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发表时间：
2009-11
期刊：
影响因子：
29.4
通讯作者：
Blumberg RS
中科院分区：
文献类型：
--
作者：
Kobayashi K;Qiao SW;Yoshida M;Baker K;Lencer WI;Blumberg RS
新生儿免疫球蛋白（IG）G受体（FcRn）可保护实质细胞和造血细胞中的单体IgG免受卡他霉素的影响。在树突状细胞中，FcRn还促进与IgG相关的抗原呈递。由于具有抗菌特异性的IgG是炎症性肠病的标志，我们试图确定其意义和与抗原呈递细胞中FcRn表达的关系，重点是鞭毛蛋白特异性IgG。在野生型和FcRn−/−小鼠中诱导循环抗鞭毛蛋白IgG水平，然后用葡聚糖硫酸钠（DSS）诱导结肠炎。使用骨髓嵌合体模型来定位FcRn作用的位点。与接受对照IgG的小鼠相比，接受抗鞭毛蛋白IgG的野生型小鼠在施用DSS后表现出更严重的结肠炎。用鞭毛蛋白免疫的野生型小鼠对DSS给药的反应比在类似处理的FcRn−/−小鼠中观察到的结肠炎显著更严重。在嵌合体研究中，给予野生型骨髓并用鞭毛蛋白免疫的FcRn−/−小鼠比给予FcRn−/−骨髓并用鞭毛蛋白免疫的野生型小鼠表现出显著更多的结肠炎。两组嵌合小鼠的血清抗鞭毛蛋白IgG水平相似，这与造血细胞和非造血细胞同等参与FcRn介导的IgG保护一致。抗细菌IgG抗体参与结肠炎的发病机制;该途径需要抗原呈递细胞（表达FcRn的造血细胞的主要亚群）中的FcRn。
The neonatal receptor for immunoglobulin (Ig)G (FcRn) protects monomeric IgG from catabolism in parenchymal and hematopoietic cells. In dendritic cells, FcRn also promotes presentation of antigens in association with IgG. Since IgGs with anti-bacterial specificity are a hallmark of inflammatory bowel disease, we sought to determine their significance and relationship to FcRn expression in antigen presenting cells, focusing on IgGs specific for flagellin. Levels of circulating anti-flagellin IgG were induced in wild-type and FcRn−/− mice, followed by induction of colitis with dextran sodium sulfate (DSS). Bone marrow chimera models were used to localize the site of FcRn action. Wild-type mice that received anti-flagellin IgG exhibited more severe colitis following administration of DSS, compared to mice that received control IgG. Wild-type mice immunized with flagellin exhibited significantly more severe colitis in response to DSS administration than that observed in similarly treated FcRn−/− mice. In chimera studies, FcRn−/− mice given wild-type bone marrow and immunized with flagellin exhibited significantly more colitis than wild-type mice given FcRn−/− bone marrow and immunized with flagellin. Serum anti-flagellin IgG levels were similar in both sets of chimeric mice, consistent with the equal participation of hematopoietic and non-hematopoeitic cells in FcRn-mediated IgG protection. Anti-bacterial IgG antibodies are involved in the pathogenesis of colitis; this pathway requires FcRn in antigen presenting cells, the major subset of hematopoietic cells that express FcRn.
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影响因子：
29.4
作者：
Landers, CJ;Cohavy, O;Targan, SR
通讯作者：
Targan, SR
影响因子：
6.7
作者：
Axelsson, LG;Landstrom, E;BylundFellenius, AC
通讯作者：
BylundFellenius, AC
DOI：
10.1073/pnas.93.11.5512
发表时间：
1996-05-28
影响因子：
11.1
作者：
Junghans, RP;Anderson, CL
通讯作者：
Anderson, CL
影响因子：
15.9
作者：
Akilesh, S;Petkova, S;Roopenian, D
通讯作者：
Roopenian, D
影响因子：
15.9
作者：
Dickinson, BL;Badizadegan, K;Lencer, WI
通讯作者：
Lencer, WI