Death receptor 3 is essential for generating optimal protective CD41 T-cell immunity against Salmonella
Death receptor 3 is essential for generating optimal protective CD41 T-cell immunity against Salmonella
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DOI：
10.1002/eji.201041950
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发表时间：
2012-03-01
影响因子：
5.4
通讯作者：
Al-Shamkhani, Aymen
中科院分区：
文献类型：
--
作者：
Buchan, Sarah L.;Taraban, Vadim Y.;Al-Shamkhani, Aymen
TNF受体超家族成员死亡受体3（DR 3）加剧了Th 2和Th 17细胞介导的炎症和自身免疫性疾病，但尚未报道在宿主防御中的作用。在这里，我们研究的作用DR 3感染肠道沙门氏菌血清型鼠伤寒。感染导致DR 3配体TL 1A的延长表达，但不导致相关的TNF超家族蛋白OX 40 L或CD 30 L的延长表达。TL 1A表达定位于脾F4/80+巨噬细胞，S.肠伤寒复制，并在时间上与CD 4+细胞扩增的开始相一致。为了解决TL 1A-DR 3相互作用的相关性，我们检测了对S.缺乏DR 3的小鼠中的肠伤寒沙门氏菌。与WT小鼠相比，感染的DR 3-/-小鼠具有减少数量的抗原经历和增殖的CD 4 + T细胞。此外，IFN-？+ DR 3-/-小鼠中的CD 4 + T细胞在整个细菌清除时间内较低。重要的是，依赖于Th 1细胞的细菌清除在DR 3-/-小鼠中也受损。这种缺陷是CD 4 + T细胞固有的，如接受DR 3-/-CD 4 + T细胞的RAG 2缺陷小鼠与WT CD 4+细胞接受者相比细菌负荷增加所证明的。这些数据首次确立了DR 3在宿主防御反应中的作用。
The TNF receptor superfamily member death receptor 3 (DR3) exacerbates Th2- and Th17-cell-mediated inflammatory and autoimmune conditions, yet no role in host defence has been reported. Here, we examined the role of DR3 during infection with Salmonella enterica serovar Typhimurium. Infection resulted in protracted expression of the DR3 ligand TL1A but not the related TNF superfamily proteins OX40L or CD30L. TL1A expression was localized to splenic F4/80+ macrophages where S. enterica Typhimurium replicates, and temporally coincided with the onset of CD4+-cell expansion. To address the relevance of the TL1A-DR3 interaction, we examined immune responses to S. enterica Typhimurium in mice lacking DR3. Infected DR3-/- mice harboured reduced numbers of antigen-experienced and proliferating CD4+ T cells compared with WT mice. Furthermore, the frequency of IFN-?+ CD4+ T cells in DR3-/- mice was lower throughout the time of bacterial clearance. Importantly, bacterial clearance, which is dependent on Th1 cells, was also impaired in DR3-/- mice. This defect was intrinsic to CD4+ T cells as evidenced by an increase in bacterial burden in RAG2-deficient mice receiving DR3-/- CD4+ T cells compared with WT CD4+-cell recipients. These data establish for the first time a role for DR3 in a host defence responce.