ORIGINAL ARTICLE
Targeting NF-κB c-Rel in regulatory T cells to treat corneal transplantation rejection

https://doi.org/10.1111/ajt.16760Get rights and content
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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.

KEYWORDS

basic (laboratory) research
corneal transplantation
graft survival
immune modulation
immunosuppression
ophthalmology
rejection
rejection: T cell mediated (TCMR)
science
T cell biology

Abbreviations

aTregs
activated Tregs
ChIP
chromatin immuno-precipitation
CLNs
cervical lymph nodes
DTR
diphtheria toxin receptor
ECAR
extracellular acidification rate
TCR
T cell receptor
Teff
effector T cells
Treg
regulatory T cells
tTreg
thymic Tregs

Cited by (0)

Jiang Bian and Ting Wang contributed equally to this work.