Release of Active TGF-β1 from the Latent TGF-β1/GARP Complex on T Regulatory Cells Is Mediated by Integrin β8
Copyright policy )Release of Active TGF-β1 from the Latent TGF-β1/GARP Complex on T Regulatory Cells Is Mediated by Integrin β8
Abstract Activated T regulatory cells (Tregs) express latent TGF-β1 on their cell surface bound to GARP. Although integrins have been implicated in mediating the release of active TGF-β1 from the complex of latent TGF-β1 and latent TGF-β1 binding protein, their role in processing latent TGF-β1 from the latent TGF-β1/GARP complex is unclear. Mouse CD4+Foxp3+ Treg, but not CD4+Foxp3− T cells, expressed integrin β8 (Itgb8) as detected by quantitative RT-PCR. Itgb8 expression was a marker of thymically derived (t)Treg, because it could not be detected on Foxp3+Helios− Tregs or on Foxp3+ T cells induced in vitro. Tregs from Itgb8 conditional knockouts exhibited normal suppressor function in vitro and in vivo in a model of colitis but failed to provide TGF-β1 to drive Th17 or induced Treg differentiation in vitro. In addition, Itgb8 knockout Tregs expressed higher levels of latent TGF-β1 on their cell surface consistent with defective processing. Thus, integrin αvβ8 is a marker of tTregs and functions in a cell intrinsic manner in mediating the processing of latent TGF-β1 from the latent TGF-β1/GARP complex on the surface of tTregs.
- National Institute of Health Pakistan
- National Institute of Allergy and Infectious Diseases United States
- National Institutes of Health United States
Mice, Knockout, Integrins, Integrin beta Chains, Green Fluorescent Proteins, Membrane Proteins, Cell Differentiation, Forkhead Transcription Factors, Colitis, Lymphocyte Activation, T-Lymphocytes, Regulatory, DNA-Binding Proteins, Mice, Inbred C57BL, Transforming Growth Factor beta1, Mice, Animals, Th17 Cells, Biomarkers, Transcription Factors
Mice, Knockout, Integrins, Integrin beta Chains, Green Fluorescent Proteins, Membrane Proteins, Cell Differentiation, Forkhead Transcription Factors, Colitis, Lymphocyte Activation, T-Lymphocytes, Regulatory, DNA-Binding Proteins, Mice, Inbred C57BL, Transforming Growth Factor beta1, Mice, Animals, Th17 Cells, Biomarkers, Transcription Factors
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