Ping X, Li Y, Li J
Nanjing University School of Medicine, Research Institute of General Surgery, Jinling Hospital, Nanjing, China.
Transplant Proc. 2010 Nov;42(9):3803-8. doi: 10.1016/j.transproceed.2010.08.057.
This study investigated changes in the mucosal barrier of transplanted intestines with particular emphasis on antigen sampling by Peyer's patches (PPs).
Heterotopic small bowel transplantation (SBTx) was performed as described previously. C57BL/6 mice were used as donors and BALB/c (allogeneic) or C57BL/6 mice (syngeneic) as recipients. Tacrolimus (FK506) or saline control was administered to the recipients for 2 weeks. Four groups included in this study were: syngeneic with or without immunosuppression (SYN and SYN + FK506, respectively) and allogeneic with or without immunosuppression (ALLO and ALLO + FK506, respectively). Animals were sacrificed weekly after SBTx to evaluate microfold (M) cells within PPs and for routine histology. By the third postoperative week, recipients were subjected to an intestine loop model to examine the uptake of microbeads by M cells as well as expression of Toll-like receptor 2 (TLR2) protein in the PPs with or without a TLR2 agonist challenge. We also measured occludin expression on follicle-associated epithelium (FAE) of PPs in the grafts.
Transportation of microbeads through the PPs of the grafts increased in the ALLO + FK506 group compared with that in the SYN or SYN + FK506 group. This finding was accompanied by increased expression of TLR2 in the PPs and a gradually increased number of M cells following SBTx. However, occludin expression patterns on the FAE of the PPs in the grafts were similar among SYN, SYN + FK506, and ALLO + FK506 groups. Nevertheless, as transportation of microbeads and TLR2 expression in the PPs of the grafts was enhanced once exposed to Pam3Cys-SKKKK, similar results were not seen in the ALLO + FK506 group.
Our study revealed that the mucosal barrier of intestinal grafts is altered under alloreactivity as evidenced by enhanced antigen sampling. Such a change may provide a pathway for translocation of microorganisms in the lumen.
本研究调查了移植肠黏膜屏障的变化，特别关注派尔集合淋巴结（PPs）的抗原采样情况。
按照先前描述的方法进行异位小肠移植（SBTx）。以C57BL/6小鼠作为供体，BALB/c小鼠（同种异体）或C57BL/6小鼠（同基因）作为受体。受体给予他克莫司（FK506）或生理盐水对照，持续2周。本研究纳入的四组分别为：同基因有或无免疫抑制组（分别为SYN和SYN + FK506）以及同种异体有或无免疫抑制组（分别为ALLO和ALLO + FK506）。SBTx后每周处死动物，以评估PPs内的微褶（M）细胞并进行常规组织学检查。术后第三周，将受体置于肠袢模型中，以检查M细胞对微珠的摄取以及在有或无TLR2激动剂刺激情况下PPs中Toll样受体2（TLR2）蛋白的表达。我们还测量了移植物中PPs的滤泡相关上皮（FAE）上闭合蛋白的表达。
与SYN或SYN + FK506组相比，ALLO + FK506组移植物中PPs对微珠的转运增加。这一发现伴随着PPs中TLR2表达增加以及SBTx后M细胞数量逐渐增加。然而，SYN、SYN + FK506和ALLO + FK506组移植物中PPs的FAE上闭合蛋白的表达模式相似。尽管如此，一旦暴露于Pam3Cys - SKKKK，移植物中PPs的微珠转运和TLR2表达增强，但ALLO + FK506组未出现类似结果。
我们的研究表明，在同种异体反应性情况下，肠移植物的黏膜屏障会发生改变，抗原采样增强即为证据。这种变化可能为管腔内微生物的易位提供一条途径。
