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
- single cell
- induced apoptosis
- lymph node
- cell therapy
- nk cells
- regulatory t cells
- dendritic cells
- cell cycle arrest
- cell death
- poor prognosis
- palliative care
- magnetic resonance imaging
- working memory
- mesenchymal stem cells
- endoplasmic reticulum stress
- computed tomography
- cell proliferation
- genome wide
- dna methylation
- bone marrow
- quantum dots
- long non coding rna
- neoadjuvant chemotherapy
- contrast enhanced
- pi k akt