Retinoic acid signaling during priming licenses intestinal CD103+ CD8 TRM cell differentiation.
Zhijuan QiuCamille KhairallahTimothy H ChuJessica N ImperatoXinyuan LeiGalina RomanovAmha AtakilitLynn PuddingtonBrian S SheridanPublished in: The Journal of experimental medicine (2023)
CD8 tissue-resident memory T (TRM) cells provide frontline protection at barrier tissues; however, mechanisms regulating TRM cell development are not completely understood. Priming dictates the migration of effector T cells to the tissue, while factors in the tissue induce in situ TRM cell differentiation. Whether priming also regulates in situ TRM cell differentiation uncoupled from migration is unclear. Here, we demonstrate that T cell priming in the mesenteric lymph nodes (MLN) regulates CD103+ TRM cell differentiation in the intestine. In contrast, T cells primed in the spleen were impaired in the ability to differentiate into CD103+ TRM cells after entry into the intestine. MLN priming initiated a CD103+ TRM cell gene signature and licensed rapid CD103+ TRM cell differentiation in response to factors in the intestine. Licensing was regulated by retinoic acid signaling and primarily driven by factors other than CCR9 expression and CCR9-mediated gut homing. Thus, the MLN is specialized to promote intestinal CD103+ CD8 TRM cell development by licensing in situ differentiation.
Keyphrases
- induced apoptosis
- single cell
- lymph node
- dendritic cells
- cell therapy
- cell cycle arrest
- regulatory t cells
- nk cells
- gene expression
- stem cells
- magnetic resonance
- immune response
- palliative care
- cell death
- genome wide
- early stage
- endoplasmic reticulum stress
- copy number
- oxidative stress
- signaling pathway
- cell proliferation
- transcription factor
- binding protein