小柯机器人

瑞士苏黎世大学Christian Stockmann团队近日取得重要工作进展，他们研究开发了基于疫苗的免疫疗法靶向肝和肺中的促纤维化细胞。这一研究成果2022年9月15日在线发表于《细胞—干细胞》杂志上。

研究人员测试了针对在成纤维细胞中强烈表达但在静息成纤维细胞中高度受限的内源性蛋白质的特异性免疫，能否引发抗原特异性细胞毒性T细胞反应以改善器官纤维化。计算机表位预测表明，促纤维化细胞中基因Adam12和Gli1的激活以及由此产生的“自身肽”可用于T细胞疫苗，以消融纤维化细胞。研究人员证明了疫苗接种方法对启动CD8⁺ T细胞反应的功效，从而减少小鼠肝脏和肺中的成纤维细胞和纤维化。这些结果为基于疫苗接种的免疫疗法治疗纤维化提供了原理证明。

据介绍，纤维化几乎是每一种慢性疾病的最终途径，无论其发病机制如何。在慢性损伤时，活化的成纤维细胞会沉积过多的细胞外基质，几乎任何器官都可能发生严重的组织纤维化。然而，针对成纤维细胞而保留健康组织内稳态成纤维细胞的抗纤维化治疗是有限的。

附：英文原文

Title: Vaccination-based immunotherapy to target profibrotic cells in liver and lung

Author: Michal Sobecki, Jing Chen, Ewelina Krzywinska, Shunmugam Nagarajan, Zheng Fan, Eric Nelius, Josep M. Monné Rodriguez, Frauke Seehusen, Amro Hussein, Greta Moschini, Edries Y. Hajam, Ravi Kiran, Dagmar Gotthardt, Julien Debbache, Cécile Badoual, Tatsuyuki Sato, Takayuki Isagawa, Norihiko Takeda, Corinne Tanchot, Eric Tartour, Achim Weber, Sabine Werner, Johannes Loffing, Lukas Sommer, Veronika Sexl, Christian Münz, Carol Feghali-Bostwick, Elena Pachera, Oliver Distler, Jess Snedeker, Colin Jamora, Christian Stockmann

Issue&Volume: 2022-09-15

Abstract: Fibrosis is the final path of nearly every form of chronic disease, regardless of the pathogenesis. Upon chronic injury, activated, fibrogenic fibroblasts deposit excess extracellular matrix, and severe tissue fibrosis can occur in virtually any organ. However, antifibrotic therapies that target fibrogenic cells, while sparing homeostatic fibroblasts in healthy tissues, are limited. We tested whether specific immunization against endogenous proteins, strongly expressed in fibrogenic cells but highly restricted in quiescent fibroblasts, can elicit an antigen-specific cytotoxic T cell response to ameliorate organ fibrosis. In silico epitope prediction revealed that activation of the genes Adam12 and Gli1 in profibrotic cells and the resulting “self-peptides” can be exploited for T cell vaccines to ablate fibrogenic cells. We demonstrate the efficacy of a vaccination approach to mount CD8+ T cell responses that reduce fibroblasts and fibrosis in the liver and lungs in mice. These results provide proof of principle for vaccination-based immunotherapies to treat fibrosis.

DOI: 10.1016/j.stem.2022.08.012

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(22)00376-9#%20

Cell Stem Cell：《细胞—干细胞》，创刊于2007年。隶属于细胞出版社，最新IF：25.269
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