Hjelmström P, Fjell J, Nakagawa T, Sacca R, Cuff C A, Ruddle N H
Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut 06520-8034, USA.
Am J Pathol. 2000 Apr;156(4):1133-8. doi: 10.1016/S0002-9440(10)64981-4.
Secondary lymphoid tissue chemokine (SLC) and B lymphocyte chemoattractant (BLC) are homing chemokines that have been implicated in the trafficking of lymphocytes and dendritic cells in lymphoid organs. Lymphotoxin-alpha (LTalpha), a cytokine crucial for development of lymphoid organs, is important for expression of SLC and BLC in secondary lymphoid organs during development. Here we report that transgenic expression of LTalpha induces inflammation and ectopic expression of SLC and BLC in the adult animal. LTbeta was not necessary for induction of BLC and SLC in inflamed tissues, whereas, in contrast, tumor necrosis factor receptor-1 was found to be important for the LTalpha-mediated induction of these chemokines. The ectopic expression of LTalpha is associated with a chronic inflammation that closely resembles organized lymphoid tissue and this lymphoid neogenesis can also be seen in several chronic inflammatory diseases, including in the pancreas of the prediabetic nonobese diabetic (NOD) mouse. Expression of SLC was also observed in the pancreas of prediabetic NOD mice. This study implicates BLC and SLC in chronic inflammation and presents further evidence that LTalpha orchestrates lymphoid organogenesis both during development and in inflammatory processes.
二级淋巴组织趋化因子(SLC)和B淋巴细胞趋化因子(BLC)是归巢趋化因子,与淋巴细胞和树突状细胞在淋巴器官中的运输有关。淋巴毒素-α(LTα)是一种对淋巴器官发育至关重要的细胞因子,在发育过程中对二级淋巴器官中SLC和BLC的表达很重要。在此我们报告,LTα的转基因表达在成年动物中诱导炎症以及SLC和BLC的异位表达。LTβ对于炎症组织中BLC和SLC的诱导并非必需,而相反,发现肿瘤坏死因子受体-1对于LTα介导的这些趋化因子的诱导很重要。LTα的异位表达与一种类似于有组织的淋巴组织的慢性炎症相关,并且这种淋巴新生也可见于几种慢性炎症性疾病,包括在糖尿病前期非肥胖糖尿病(NOD)小鼠的胰腺中。在糖尿病前期NOD小鼠的胰腺中也观察到了SLC的表达。本研究表明BLC和SLC与慢性炎症有关,并进一步证明LTα在发育过程和炎症过程中都协调淋巴器官的发生。