Mar 9, 2020

Single-cell transcriptomics of allo-reactive CD4+ T cells over time reveals divergent fates during gut GVHD

bioRxiv
Jessica A EngelAshraful Haque

Abstract

Acute gastrointestinal Graft-versus-Host Disease is a primary determinant of mortality after allogeneic hematopoietic stem cell transplantation (alloSCT). It is mediated by alloreactive donor CD4+ T cells that differentiate into pathogenic subsets expressing IFNγ, IL-17A or GM-CSF, and is regulated by subsets expressing IL-10 and/or Foxp3. Developmental relationships between T-helper states during priming in mesenteric lymph nodes (mLN) and effector function in the GI tract remain undefined at genome-scale. We used scRNA-seq and computational modelling to create an atlas of putative differentiation pathways during GVHD. Computational trajectory inference suggested emergence of pathogenic and regulatory states along a single developmental trajectory in mLN. Importantly, we identified an unexpected second trajectory, categorised by little proliferation or cytokine expression, reduced glycolysis, and high TCF1 expression. TCF1hi cells upregulated α4β7 prior to gut migration and failed to express cytokines therein. Nevertheless, they demonstrated recall potential and plasticity following secondary transplantation, including cytokine or Foxp3 expression, but reduced TCF1. Thus, scRNA-seq revealed divergence of allo-reactive CD4+ T c...Continue Reading

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Mentioned in this Paper

C-reactive protein
Protein Expression
Lymph Node of Mesentery
Foxp3 protein, mouse
Allogeneic Hematopoietic Stem Cell Transplantation
Migration, Cell
Graft-vs-Host Disease
Transplantation
Finding
CD4 Positive T Lymphocytes

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