Homeostatic regulation of T cell trafficking by a B cell-derived peptide is impaired in autoimmune and chronic inflammatory disease.
Homeostatic regulation of T cell trafficking by a B cell-derived peptide is impaired in autoimmune and chronic inflammatory disease.
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DOI：
10.1038/nm.3842
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发表时间：
2015-05
期刊：
影响因子：
82.9
通讯作者：
Rainger GE
中科院分区：
文献类型：
--
作者：
Chimen M;McGettrick HM;Apta B;Kuravi SJ;Yates CM;Kennedy A;Odedra A;Alassiri M;Harrison M;Martin A;Barone F;Nayar S;Hitchcock JR;Cunningham AF;Raza K;Filer A;Copland DA;Dick AD;Robinson J;Kalia N;Walker LSK;Buckley CD;Nash GB;Narendran P;Rainger GE
在炎症反应期间，必须严格控制淋巴细胞向组织中的募集，因为失调的运输有助于慢性疾病的发病机制。在此，我们发现在炎症过程中和对脂联素的应答中，B细胞通过分泌一种蛋白水解衍生自14.3.3. δ蛋白的肽（PEPITEM）来紧张性抑制T细胞的运输。PEPITEM结合内皮细胞上的钙粘蛋白-15，促进鞘氨醇-1磷酸的合成和释放，其抑制T细胞的运输而不影响其他白细胞的募集。脂联素受体在B细胞上的表达和脂联素诱导的PEPITEM分泌随着年龄的增长而减弱，这意味着该途径的免疫衰老。此外，这些变化在患有1型糖尿病或类风湿性关节炎的个体中是明显的，并且与健康年龄匹配的供体相比，患者血清中的循环PEPITEM减少。在这两种疾病中，T细胞穿过发炎内皮的运输的紧张性抑制丧失。重要的是，通过外源性PEPITEM重新建立对患者T细胞运输的控制。此外，在腹膜炎、肝I/R损伤、沙门氏菌感染、葡萄膜炎和舍格伦综合征的动物模型中，PEPITEM可以减少T细胞向炎症组织中的募集。
During an inflammatory response, lymphocyte recruitment into tissue must be tightly controlled because dysregulated trafficking contributes to the pathogenesis of chronic disease. Here we show that during inflammation and in response to adiponectin, B cells tonically inhibit T cell trafficking by secreting a peptide (PEPITEM) proteolytically derived from 14.3.3.ζδ protein. PEPITEM binds cadherin-15 on endothelial cells, promoting synthesis and release of sphingosine-1 phosphate, which inhibits trafficking of T cells without affecting recruitment of other leukocytes. Expression of adiponectin receptors on B cells and adiponectin induced PEPITEM secretion wanes with age, implying immune senescence of the pathway. Additionally, these changes are evident in individuals with type-1-diabetes or rheumatoid arthritis, and circulating PEPITEM in patient serum is reduced compared to healthy age matched donors. In both diseases, tonic inhibition of T cell trafficking across inflamed endothelium is lost. Importantly, control of patient T cell trafficking is re-established by exogenous PEPITEM. Moreover, in animal models of peritonitis, hepatic I/R injury, Salmonella infection, Uveitis and Sjögren’s Syndrome, PEPITEM could reduce T cell recruitment into inflamed tissues.
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影响因子：
4.4
作者：
CHEN, JZ;TROUNSTINE, M;HUSZAR, D
通讯作者：
HUSZAR, D
影响因子：
3.5
作者：
Finnegan, Alison;Ashaye, Susan;Hamel, Keith M.
通讯作者：
Hamel, Keith M.
影响因子：
4.4
作者：
Flores-Langarica, Adriana;Marshall, Jennifer L.;Cunningham, Adam F.
通讯作者：
Cunningham, Adam F.
DOI：
10.4049/jimmunol.1201216
发表时间：
2012-10-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Bombardieri M;Barone F;Lucchesi D;Nayar S;van den Berg WB;Proctor G;Buckley CD;Pitzalis C
通讯作者：
Pitzalis C
影响因子：
4.8
作者：
Garcia-Guzman, M;Dolfi, F;Vuori, K
通讯作者：
Vuori, K