INDUCTION OF SKIN FIBROSIS AND AUTOANTIBODIES BY INFUSION OF IMMUNOCOMPETENT CELLS FROM TIGHT-SKIN MICE INTO C57BL/6 PA/PA MICE
INDUCTION OF SKIN FIBROSIS AND AUTOANTIBODIES BY INFUSION OF IMMUNOCOMPETENT CELLS FROM TIGHT-SKIN MICE INTO C57BL/6 PA/PA MICE
复制标题
DOI：
10.1006/jaut.1993.1059
复制
发表时间：
1993-12-01
影响因子：
12.8
通讯作者：
BONA, CA
中科院分区：
文献类型：
--
作者：
PHELPS, RG;DAIAN, C;BONA, CA
皮肤紧绷（TSK/+）小鼠会出现与硬皮病特征性自身抗体的出现相关的皮肤增生。为了研究自身免疫在皮肤纤维化产生中的作用，我们进行了过继移植实验，其中将TSK/pa小鼠的骨髓细胞输注到pa/pa小鼠同窝小鼠中。 （C57BL/6 pa/pa 小鼠用于产生杂合子 TSK/pa 小鼠。）我们的结果表明，在几个月的前驱期后，骨髓细胞的转移导致皮肤纤维化、自身抗体的存在以及 (α1) 胶原蛋白 I 和 TGFβ 基因的转录增加。单独输注富集的 B 或 T 细胞不会引起皮肤纤维化，但单独输注 B 细胞会增加自身抗体的产生。相比之下，T 和 B 淋巴细胞的转移会导致早期轻度纤维化、细胞浸润和自身抗体产生，以及 (α1) 胶原蛋白基因的转录增加。我们的结果首次有力地证明，免疫活性细胞可以在激活胶原蛋白合成导致皮肤纤维化中发挥作用。
Tight skin (TSK/+) mice develop a cutaneous hyperplasia associated with the occurrence of autoantibodies characteristic for scleroderma. In order to study the role of autoimmunity in the production of skin fibrosis, we conducted adoptive transfer experiments in which bone marrow cells of TSK/pa mice were infused into pa/pa mice littermates. (C57BL/6 pa/pa mice are used to produce heterozygous TSK/pa mice.) Our results showed that after a prodromal period of several months, the transfer of bone marrow cells led to skin fibrosis, the presence of autoantibodies, and increased transcription of (α1) collagen I and TGFβ genes. Infusion of enriched B or T cells alone did not cause skin fibrosis but of B cells alone increased autoantibody production.By contrast, transfer of T and B lymphocytes led to earlier mild fibrosis, cellular infiltration and autoantibody production as well as increased transcription of the (α1) collagen gene. Our results strongly demonstrate, for the first time, that immunocompetent cells can play a role in the activation of collagen synthesis leading to skin fibrosis.