Shift of graft-versus-host-disease target organ tropism by dietary vitamin A.
Shift of graft-versus-host-disease target organ tropism by dietary vitamin A.
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DOI：
10.1371/journal.pone.0038252
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Förster R
中科院分区：
文献类型：
--
作者：
Koenecke C;Prinz I;Bubke A;Schreder A;Lee CW;Pabst O;Förster R
供体T细胞的肠道归巢是异基因造血干细胞移植受者发生肠道移植物抗宿主病的原因。肠道特异性归巢受体整合素-α4、趋化因子受体β7和趋化因子受体CCR9在肠道相关淋巴组织(GALT)的表达受维生素A代谢产物维甲酸的影响。在这里，我们讨论了在实验性GvHD过程中，维生素A缺乏在HSCT受者供体T细胞迁移中的作用。用维生素A缺乏的饲料喂养维生素A缺乏(VAD)小鼠。实验在C57BL/6转BALB/c急性移植物抗宿主病模型上进行。我们发现异基因移植后α-β4、CCR7和CCR9在GALT中的表达减少。体内竞争性归巢试验表明，VAD小鼠体内的同种异体T细胞不像标准饮食(STD)小鼠中的T细胞那样高效地归巢到肠道。VAD-HSCT受者的GvHD病程得到改善，因此，与接受STD的受者相比，他们的生存期延长。然而，VAD的接受者没有得到保护，最终死于临床GvHD。我们发现，VAD受者肠道中供体T细胞的数量减少，但其他器官中的细胞数量和组织损伤增加。此外，我们观察到与STD受者相比，VAD患者总供者γ+T细胞中干扰素-CD4+和FoxP3+CD4+的频率较高。综上所述，这些结果表明，HSCT受者膳食维生素A缺乏改变了GvHD的靶器官取向，但也导致了HSCT后的致命性炎症。
Gut-homing of donor T cells is causative for the development of intestinal GvHD in recipients of allogeneic hematopoietic stem cell transplantation (HSCT). Expression of the gut-specific homing receptors integrin-α4β7 and chemokine receptor CCR9 on T cells is imprinted in gut-associated lymphoid tissues (GALT) under the influence of the vitamin A metabolite retinoic acid. Here we addressed the role of vitamin A deficiency in HSCT-recipients for donor T cell migration in the course of experimental GvHD. Vitamin A-deficient (VAD) mice were prepared by feeding them a vitamin A-depleted diet. Experiments were performed in a C57BL/6 into BALB/c model of acute GvHD. We found that expression of integrin-α4β7 and CCR9 in GALT was reduced in VAD recipients after HSCT. Competitive in vivo homing assays showed that allogeneic T cells primed in VAD mice did not home as efficiently to the intestine as T cells primed in mice fed with standard diet (STD). The course of GvHD was ameliorated in VAD HSCT-recipients and, consequently, their survival was prolonged compared to recipients receiving STD. However, VAD-recipients were not protected and died of clinical GvHD. We found reduced numbers of donor T cells in the intestine but increased cell counts and tissue damage in other organs of VAD-recipients. Furthermore, we observed high IFN-γ+CD4+ and low FoxP3+CD4+ frequencies of total donor CD4+ T cells in VAD as compared to STD recipients. Taken together, these results indicate that dietary vitamin A deficiency in HSCT-recipients changed target organ tropism in GvHD but also resulted in fatal inflammation after HSCT.
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DOI：
10.1084/jem.20080039
发表时间：
2008-10-27
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hammerschmidt SI;Ahrendt M;Bode U;Wahl B;Kremmer E;Förster R;Pabst O
通讯作者：
Pabst O
影响因子：
29.4
作者：
Kang SG;Wang C;Matsumoto S;Kim CH
通讯作者：
Kim CH
DOI：
10.1084/jem.20011502
发表时间：
2002-01-07
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Campbell DJ;Butcher EC
通讯作者：
Butcher EC
影响因子：
20.3
作者：
Beilhack, A;Schulz, S;Negrin, RS
通讯作者：
Negrin, RS
影响因子：
5.4
作者：
Koenecke, Christian;Chennupati, Vijaykumar;Prinz, Immo
通讯作者：
Prinz, Immo