Mice have frequently been used to model human diseases involving immune dysregulation such as autoimmune and inflammatory diseases.These models help elucidatethe mechanisms underlying the disease and in the developmen...Mice have frequently been used to model human diseases involving immune dysregulation such as autoimmune and inflammatory diseases.These models help elucidatethe mechanisms underlying the disease and in the development of novel therapies.However,if mice are deficient in certain cells and/or effectors associated with human diseases,how can their functions be investigated in this species?Mucosal-associated invariant T(MAIT)cells,a novel innate-like T cell family member,are a good example.MAIT cells are abundant in humans but scarce in laboratory mice.MAIT cells harbor an invariant T cell receptor and recognize nonpeptidic antigens vitamin B2metabolites from bacteria and yeasts.Recent studies have shown that MAIT cells play a pivotal role in human diseases such as bacterial infections and autoimmune and inflammatory diseases.MAIT cells possess granulysin,a human-specific effector molecule,but granulysin and its homologue are absent in mice.Furthermore,MAIT cells show poor proliferation in vitro.To overcome these problems and further our knowledge of MAIT cells,we have established a method to expand MAIT cells via induced pluripotent stem cells(iP SCs).In this review,we describe recent advances in the field of MAIT cell research and our approach for human disease modeling with iP SCderived MAIT cells.展开更多
Numerous efforts have been attempted to regenerate T cells in culture dish from pluripotent stem cells(PSCs).However,in vitro generated T cells exhibited extremely low activity and compromised immunocompetency in vivo...Numerous efforts have been attempted to regenerate T cells in culture dish from pluripotent stem cells(PSCs).However,in vitro generated T cells exhibited extremely low activity and compromised immunocompetency in vivo.Here,we describe a two-step protocol for regenerating functional T cells using an inducible Runx1-Hoxa9-PSC(iR9-PSCs)line.The procedure mainly includes generation of induced hematopoietic progenitor cells(iHPCs)in vitro,transplantation,and development of functional induced T cells(iT)in vivo via transplantation.The entire induction process in vitro requires 21 days before iHPCs transplantation.The development of mature T cells in vivo takes 4 to 6 weeks post-transplantation.We provide a simple and reproducible approach for functional T cell regeneration from iR9-PSCs for research purpose.展开更多
文摘Mice have frequently been used to model human diseases involving immune dysregulation such as autoimmune and inflammatory diseases.These models help elucidatethe mechanisms underlying the disease and in the development of novel therapies.However,if mice are deficient in certain cells and/or effectors associated with human diseases,how can their functions be investigated in this species?Mucosal-associated invariant T(MAIT)cells,a novel innate-like T cell family member,are a good example.MAIT cells are abundant in humans but scarce in laboratory mice.MAIT cells harbor an invariant T cell receptor and recognize nonpeptidic antigens vitamin B2metabolites from bacteria and yeasts.Recent studies have shown that MAIT cells play a pivotal role in human diseases such as bacterial infections and autoimmune and inflammatory diseases.MAIT cells possess granulysin,a human-specific effector molecule,but granulysin and its homologue are absent in mice.Furthermore,MAIT cells show poor proliferation in vitro.To overcome these problems and further our knowledge of MAIT cells,we have established a method to expand MAIT cells via induced pluripotent stem cells(iP SCs).In this review,we describe recent advances in the field of MAIT cell research and our approach for human disease modeling with iP SCderived MAIT cells.
基金This work was supported by grants from the Strategic Priority Research Program of Chinese Academy of Sciences(XDA16010601)the Health and Medical Care Collaborative Innovation Program of Guangzhou Scientific and Technology(201803040017)+4 种基金the CAS Key Research Program of Frontier Sciences(QYZDB-SSW-SMC057)the National Key R&D Program of China(2019YFA0110200)the Major Research and Development Project of Guangzhou Regenerative Medicine and Health Guangdong Laboratory(2018GZR110104006)the Science and Technology Planning Project of Guangdong Province(2017B030314056)the grants from the National Natural Science Foundation of China(Grant No 81925002).
文摘Numerous efforts have been attempted to regenerate T cells in culture dish from pluripotent stem cells(PSCs).However,in vitro generated T cells exhibited extremely low activity and compromised immunocompetency in vivo.Here,we describe a two-step protocol for regenerating functional T cells using an inducible Runx1-Hoxa9-PSC(iR9-PSCs)line.The procedure mainly includes generation of induced hematopoietic progenitor cells(iHPCs)in vitro,transplantation,and development of functional induced T cells(iT)in vivo via transplantation.The entire induction process in vitro requires 21 days before iHPCs transplantation.The development of mature T cells in vivo takes 4 to 6 weeks post-transplantation.We provide a simple and reproducible approach for functional T cell regeneration from iR9-PSCs for research purpose.
