Title:Gene/Cell Therapy Approaches for Immune Dysregulation Polyendocrinopathy Enteropathy X-Linked Syndrome
Volume: 14
Issue: 6
Author(s): Laura Passerini, Francesca R. Santoni de Sio, Matthew H. Porteus and Rosa Bacchetta
Affiliation:
关键词:
自身免疫性疾病、细胞疗法、Forkhead box P3基因、基因修正、X-连锁多内分泌腺病、肠病伴免疫失调综合征
慢病毒载体、调节性T细胞
摘要: Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked (IPEX) syndrome is a rare autoimmune
disease due to mutations in the gene encoding for Forkhead box P3 (FOXP3), a transcription factor fundamental for the
function of thymus-derived (t) regulatory T (Treg) cells. The dysfunction of Treg cells results in the development of devastating
autoimmune manifestations affecting multiple organs, eventually leading to premature death in infants, if not
promptly treated by hematopoietic stem cell transplantation (HSCT). Novel gene therapy strategies can be developed for
IPEX syndrome as more definitive cure than allogeneic HSCT. Here we describe the therapeutic approaches, alternative to
HSCT, currently under development. We described that effector T cells can be converted in regulatory T cells by LVmediated
FOXP3-gene transfer in differentiated T lymphocytes. Despite FOXP3 mutations mainly affect a highly specific
T cell subset, manipulation of stem cells could be required for long-term remission of the disease. Therefore, we believe
that a more comprehensive strategy should aim at correcting FOXP3-mutated stem cells. Potentials and hurdles of both
strategies will be highlighted here.
