FOXP3 + regulatory T cells use heparanase to access IL-2 bound to ECM in inflamed tissues.

Autor:	Martinez HA; Department of Medicine, Stanford University School of Medicine; Stanford, USA., Koliesnik I; Department of Medicine, Stanford University School of Medicine; Stanford, USA., Kaber G; Department of Medicine, Stanford University School of Medicine; Stanford, USA., Reid JK; Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary; Calgary, Canada., Nagy N; Department of Medicine, Stanford University School of Medicine; Stanford, USA., Barlow G; Department of Medicine, Stanford University School of Medicine; Stanford, USA., Falk BA; Matrix Biology Program, Benaroya Research Institute; Seattle, USA., Medina CO; Department of Medicine, Stanford University School of Medicine; Stanford, USA., Hargil A; Department of Medicine, Stanford University School of Medicine; Stanford, USA., Vlodavsky I; Tumor Integrated Cancer Center, Technion-Israel Institute of Technology; Haifa, Israel., Li JP; Department of Medical Biochemistry and Microbiology, Uppsala University; Uppsala, Finland., Pérez-Cruz M; Department of Medicine, Stanford University School of Medicine; Stanford, USA., Tang SW; Department of Medicine, Stanford University School of Medicine; Stanford, USA., Meyer EH; Department of Medicine, Stanford University School of Medicine; Stanford, USA., Wrenshall LE; Department of Surgery, Boonshoft School of Medicine, Wright State University; Dayton, USA., Lord JD; Translational Research Program, Benaroya Research Institute; Seattle, USA., Garcia KC; Department of Molecular & Cellular Physiology, Stanford University; Stanford, USA., Palmer TD; Department of Neurosurgery, Stanford University School of Medicine; Stanford, USA., Steinman L; Department of Neurology and Neurological Sciences, Stanford University School of Medicine; Stanford, USA., Nepom GT; Immune Tolerance Network, Benaroya Research Institute; Seattle, USA., Wight TN; Matrix Biology Program, Benaroya Research Institute; Seattle, USA., Bollyky PL; Department of Medicine, Stanford University School of Medicine; Stanford, USA., Kuipers HF; Department of Medicine, Stanford University School of Medicine; Stanford, USA.; Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary; Calgary, Canada.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2023 Feb 27. Date of Electronic Publication: 2023 Feb 27.
DOI:	10.1101/2023.02.26.529772
Abstrakt:	FOXP3 + regulatory T cells (Treg) depend on exogenous IL-2 for their survival and function, but circulating levels of IL-2 are low, making it unclear how Treg access this critical resource in vivo . Here, we show that Treg use heparanase (HPSE) to access IL-2 sequestered by heparan sulfate (HS) within the extracellular matrix (ECM) of inflamed central nervous system tissue. HPSE expression distinguishes human and murine Treg from conventional T cells and is regulated by the availability of IL-2. HPSE -/- Treg have impaired stability and function in vivo , including the experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis. Conversely, endowing Treg with HPSE enhances their ability to access HS-sequestered IL-2 and their tolerogenic function in vivo . Together, these data identify novel roles for HPSE and the ECM in immune tolerance, providing new avenues for improving Treg-based therapy of autoimmunity. Competing Interests: Competing interests: Authors declare no competing interests.
Databáze:	MEDLINE
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