Th17 Responses to Collagen Type V, kα1-Tubulin, and Vimentin Are Present Early in Human Development and Persist Throughout Life.
Th17 Responses to Collagen Type V, kα1-Tubulin, and Vimentin Are Present Early in Human Development and Persist Throughout Life.
复制标题
DOI：
10.1111/ajt.14097
复制
发表时间：
2017-04
期刊：
影响因子：
--
通讯作者：
Burlingham WJ
中科院分区：
文献类型：
--
作者：
Sullivan JA;Jankowska-Gan E;Hegde S;Pestrak MA;Agashe VV;Park AC;Brown ME;Kernien JF;Wilkes DS;Kaufman DB;Greenspan DS;Burlingham WJ
Th 17依赖性自身免疫反应可以在心脏或肺移植后发展，并且与慢性排斥的纤维闭塞形式相关。然而，所涉及的特异性自身抗原通常不同于与自身免疫性疾病相关的抗原。为了研究这些反应的基础，我们质疑TdR的去除或功能的阻断是否揭示了类似的自身抗原偏倚。我们发现，在健康人、成人PBMC、脐带血和胎儿胸腺中存在对V型胶原（Col V）、kα-1-微管蛋白和波形蛋白特异的Th 17细胞。使用合成肽和Col V三螺旋区（α1V）的重组片段，我们比较了来自健康供体的Th 17细胞与来自Col V反应性心脏和肺患者的Th 17细胞。虽然后者对α1（V）片段和肽以DR限制的方式反应良好，但健康个体的Th 17细胞对片段以DR限制的方式反应，而不是肽。Col V、kα-1-微管蛋白和波形蛋白是高度保守的、迄今未知的、预先存在的MHCII限制性Th 17应答的优选靶点。这些数据表明，心脏和肺移植后的自身免疫可能是由于控制气道和血管稳态的内在机制失调。
Th17-dependent autoimmune responses can develop after heart or lung transplantation, and are associated with fibro-obliterative forms of chronic rejection. However, the specific self-antigens involved are typically different from those associated with autoimmune disease. To investigate the basis of these responses, we questioned whether removal of Tregs or blockade of function reveals a similar auto-antigen bias. We found that Th17 cells specific for collagen type V (Col V), kα-1-tubulin, and vimentin were present in healthy, adult PBMC, cord blood, and fetal thymus. Using synthetic peptides and recombinant fragments of the Col V triple helical region (α1V), we compared Th17 cells from healthy donors with Th17 cells from Col V-reactive heart and lung patients. While the latter responded well to α1(V) fragments and peptides in a DR–restricted fashion, Th17 cells from healthy individuals responded in a DR-restricted fashion to fragments, but not to peptides. Col V, kα-1-tubulin, and vimentin are preferred targets of a highly conserved, hitherto unknown, pre-existing Th17 response that is MHCII-restricted. These data suggest that autoimmunity after heart and lung transplantation may result from dysregulation of an intrinsic mechanism controlling airway and vascular homeostasis.
登录
查看更多内容
影响因子：
20.1
作者：
Dart ML;Jankowska-Gan E;Huang G;Roenneburg DA;Keller MR;Torrealba JR;Rhoads A;Kim B;Bobadilla JL;Haynes LD;Wilkes DS;Burlingham WJ;Greenspan DS
通讯作者：
Greenspan DS
影响因子：
4.4
作者：
Goers, Trudie A.;Ramachandran, Sabarinathan;Mohanakumar, Thalachallour
通讯作者：
Mohanakumar, Thalachallour
影响因子：
20.3
作者：
Borsellino, Giovanna;Kleinewietfeld, Markus;Falk, Kirsten
通讯作者：
Falk, Kirsten
影响因子：
4.4
作者：
Kim, Connie J.;McKinnon, Lyle R.;Kaul, Rupert
通讯作者：
Kaul, Rupert
影响因子：
6.2
作者：
Jurcevic, S;Ainsworth, ME;Rose, ML
通讯作者：
Rose, ML