Woltman Andrea M, de Fijter Johan W, van der Kooij Sandra W, Jie Kim E, Massacrier Catherine, Caux Christophe, Daha Mohamed R, van Kooten Cees
Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands.
Am J Transplant. 2005 Sep;5(9):2114-25. doi: 10.1111/j.1600-6143.2005.00997.x.
Graft-infiltrating dendritic cells (DC) and alloreactive T lymphocytes play a critical role in renal allograft rejection. Renal proximal tubular epithelial cells (TEC) are considered as active players in the attraction of leukocytes during renal inflammatory responses. Macrophage inflammatory protein (MIP)-3alpha/CCL20 is a major chemokine expressed by epithelial cells that attracts immature DC. In the present study, we present evidence that also the transplanted kidney can be a major source of MIP-3alpha/CCL20. Renal transplant recipients with rejection showed significantly increased excretion of urinary MIP-3alpha/CCL20 that correlated with transplant function. The tubular staining for MIP-3alpha/CCL20 in renal biopsies of patients with rejection as well as in vitro studies with primary human TEC indicated that TEC might be responsible for the increased urinary MIP-3alpha/CCL20. Furthermore, MIP-3alpha/CCL20 produced by activated TEC was highly potent in the attraction of CD1a+CD34+-derived DC precursors. These data suggest a role for MIP-3alpha/CCL20 in amplification of the immune response during renal allograft rejection by attraction of CCR6+ inflammatory cells, which may include DC, to the site of inflammation.
移植物浸润树突状细胞（DC）和同种异体反应性T淋巴细胞在肾移植排斥反应中起关键作用。肾近端小管上皮细胞（TEC）被认为是肾炎症反应期间白细胞吸引的积极参与者。巨噬细胞炎性蛋白（MIP）-3α/CCL20是上皮细胞表达的一种主要趋化因子，可吸引未成熟DC。在本研究中，我们提供证据表明移植肾也可能是MIP-3α/CCL20的主要来源。发生排斥反应的肾移植受者尿中MIP-3α/CCL20排泄显著增加，且与移植肾功能相关。排斥反应患者肾活检中MIP-3α/CCL20的肾小管染色以及原代人TEC的体外研究表明，TEC可能是尿中MIP-3α/CCL20增加的原因。此外，活化的TEC产生的MIP-3α/CCL20在吸引CD1a+CD34+来源的DC前体方面具有高效力。这些数据表明MIP-3α/CCL20通过将CCR6+炎性细胞（可能包括DC）吸引至炎症部位，在肾移植排斥反应期间的免疫反应放大中发挥作用。
