Targeting NF‐κB c‐Rel in regulatory T cells to treat corneal transplantation rejection. Issue 12 (29th July 2021)

• Record Type: Journal Article
• Authors: Bian, Jiang; Wang, Ting; Sun, Jijun; He, Xiaozhen; Wu, Zhijiao; Zhang, Songmei; Chi, Hao; Fan, Tingting; Wang, Shaowen; Shi, Weiyun; Ruan, Qingguo
• Is Part Of: American journal of transplantation. Volume 21:Issue 12(2021)
• Page Start: 3858
• Page End: 3870
• Publication Date: 2021-07-29
• Subjects: basic (laboratory) research -- corneal transplantation -- graft survival -- immune modulation -- immunosuppression -- ophthalmology -- rejection -- rejection: T cell mediated (TCMR) -- science -- T cell biology; Transplantation of organs, tissues, etc -- Periodicals; 617.95
• DOI: 10.1111/ajt.16760
• Languages: English
• ISSNs: 1600-6135

Abstract

Abstract : The relevance of Tregs in the induction of tolerance against corneal allografts has been well established. Although it is well known that the conversion of Tregs into effector‐like cells contributes to the loss of corneal immune privilege, the underlying mechanism is still not fully understood. Using heterologous penetrating keratoplasty model, we found that Tregs from corneal allograft rejected mice (inflam‐Tregs) exhibit impaired function and characteristics of effector T cells. Further study showed that the expression of NF‐κB c‐Rel, a key mediator of effector T cell function, was significantly increased in inflam‐Tregs. Mechanistic study revealed that elevated NF‐κB c‐Rel level in inflam‐Tregs impaired Treg function through the promotion of inflammatory cytokine production and glycolysis. More importantly, we demonstrated that targeting NF‐κB c‐Rel was able to improve the immune suppressive function of inflam‐Tregs in vitro and enhance the potential of them to suppress corneal transplantation rejection. Therefore, our current study identified NF‐κB c‐Rel as a key mediator of the conversion of Tregs into effector‐like cells when under inflammatory environment. Abstract : Targeting of NF‐κB c‐Rel, an important mediator for the conversion of Tregs into effector‐like cells in an inflammatory environment, enhances the ability of Tregs to suppress corneal transplantation rejection.