FOXP3 and Its Cofactors as Targets of Immunotherapies  

作为免疫疗法靶点的FOXP3及其辅因子

作　　者：Yasuhiro Nagai Lian Lam Mark I. Greene Hongtao Zhang 

机构地区：[1]Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-4238, USA

出　　处：《Engineering》2019年第1期115-121,共7页工程（英文）

基　　金：grant supports from the Breast Cancer Research Foundation and the National Institutes of Health to M.I.Greene(RO1CA219034)

摘　　要：Forkhead box P3 (FOXP3) is a “master regulator” of regulatory T cells (Tregs), which are a subset of T cells that can suppress the antigen-specific immune reaction and that play important roles in host tolerance and immune homeostasis. It is well known that FOXP3 forms complexes with several proteins and can be regulated by various post-translational modifications (PTMs) such as acetylation, phosphorylation, ubiquitination, and methylation. As a consequence, the PTMs change the stability of FOXP3 and its capability to regulate gene expression, and eventually affect Treg activity. Although FOXP3 per se is not an ideal drug target, deacetylases, acetyltransferases, kinases, and other enzymes that regulate the PTMs of FOXP3 are potential targets to modulate FOXP3 and Treg activity. However, FOXP3 is not the only substrate for most of these enzymes;thus, unwanted ‘‘on target/off FOXP3” side effects must be considered when inhibitors to these enzymes are used. In this review, we summarize recent progress in the study of FOXP3 cofactors and PTM proteins, and potential clinical applications in autoimmunity and cancer immunity.Forkhead box P3(FOXP3) is a ‘‘master regulator" of regulatory T cells(Tregs), which are a subset of T cells that can suppress the antigen-specific immune reaction and that play important roles in host tolerance and immune homeostasis. It is well known that FOXP3 forms complexes with several proteins and can be regulated by various post-translational modifications(PTMs) such as acetylation, phosphorylation,ubiquitination, and methylation. As a consequence, the PTMs change the stability of FOXP3 and its capability to regulate gene expression, and eventually affect Treg activity. Although FOXP3 per se is not an ideal drug target, deacetylases, acetyltransferases, kinases, and other enzymes that regulate the PTMs of FOXP3 are potential targets to modulate FOXP3 and Treg activity. However, FOXP3 is not the only substrate for most of these enzymes; thus, unwanted ‘‘on target/off FOXP3" side effects must be considered when inhibitors to these enzymes are used. In this review, we summarize recent progress in the study of FOXP3 cofactors and PTM proteins, and potential clinical applications in autoimmunity and cancer immunity.

关 键 词：Treg FORKHEAD box P3 (FOXP3) POST-TRANSLATIONAL modification AUTOIMMUNE Cancer 

分 类 号：N[自然科学总论]