bioRxivBioengineeringPreprint
Immune checkpoint inhibitors amplify type 2 immune mediated repair bypro-regenerative scaffolds
Jordan T. GarciaiD, Anna RutaiD, Fei YuiD, Joscelyn C. MejíasiD, Alexis N. PeñaiD, Natalie RutkowskiiD, Elise F. Gray-GaillardiD, Constance Dubois, Christopher CherryiD, Maria BrowneiD, Katlin B. StiversiD, David R. MaestasiD, Kavita KrishnaniD, Alexander T.F. BelliD, Elana Judith FertigiD, Carisa M M CooneyiD, Damon S. CooneyiD, Patrick J. ByrneiD, Alexander T. HilleliD, Kellie Nicole SmithiD, Hongkai JiiD, Robert Anders, Drew M. PardolliD, Jennifer H. ElisseeffiD
Abstract
Extracellular matrix (ECM) scaffolds induce type 2 immunity to promote repair. Here, we show that immune cells recruited to ECM-treated murine muscle injuries and clinical soft tissue defects express immune checkpoints. Specifically, TH2 cells and regulatory T cells (Tregs) increase LAG3 expression, while macrophages express PDL2. TCR analysis and a triple-reporter strain for interleukin (IL)-13 and Treg fate-mapping suggest that Tregs in ECM-treated wounds transition into TH2-like exTregs that express LAG3. Immune checkpoint inhibition (ICI) significantly stimulated type 2 immunity in ECM-treated wounds, including increased TH2 cells, Treg transition to TH2-like exTregs, and pro-regenerative macrophages. Moreover, ICI enhanced muscle repair and reduced fibrosis in ECM-treated wounds. Collectively, these findings show Treg/TH2 plasticity in wound healing and introduce a novel ICI application to enhance immune-mediated regeneration.
- organism: mouse
- assay: bulk RNA-seq
- research focus: cell type annotation
- research focus: cell signaling & trafficking
- approach: experimental assay
- Citations
- 1
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