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Regulatory T cells ...
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Martinez, Hunter A.Stanford Univ, Sch Med, Dept Med, Stanford, CA USA.
(author)
Regulatory T cells use heparanase to access IL-2 bound to extracellular matrix in inflamed tissue
- Article/chapterEnglish2024
Publisher, publication year, extent ...
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Springer Nature,2024
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electronicrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:uu-533296
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-533296URI
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https://doi.org/10.1038/s41467-024-45012-9DOI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Although FOXP3+ regulatory T cells (Treg) depend on IL-2 produced by other cells for their survival and function, the levels of IL-2 in inflamed tissue are low, making it unclear how Treg access this critical resource. 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 in the experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis. Conversely, endowing monoclonal antibody-directed chimeric antigen receptor (mAbCAR) Treg with HPSE enhances their ability to access HS-sequestered IL-2 and their ability to suppress neuroinflammation in vivo. Together, these data identify a role for HPSE and the ECM in immune tolerance, providing new avenues for improving Treg-based therapy of autoimmunity. Regulatory T cell (Treg) maintenance and function require IL-2, yet this cytokine is only present in low levels in vivo. In this study, the authors demonstrate that that Treg use heparanase to access IL-2 bound to heparan sulfate proteoglycans in the extracellular matrix of inflamed brain tissue in mice.
Subject headings and genre
Added entries (persons, corporate bodies, meetings, titles ...)
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Koliesnik, IevgenStanford Univ, Sch Med, Dept Med, Stanford, CA USA.
(author)
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Kaber, GernotStanford Univ, Sch Med, Dept Med, Stanford, CA USA.
(author)
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Reid, Jacqueline K.Univ Calgary, Cumming Sch Med, Dept Clin Neurosci, Calgary, AB, Canada.;Univ Calgary, Cumming Sch Med, Hotchkiss Brain Inst, Calgary, AB, Canada.;Univ Calgary, Cumming Sch Med, Snyder Inst Chron Dis, Calgary, AB, Canada.
(author)
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Nagy, NadineStanford Univ, Sch Med, Dept Med, Stanford, CA USA.
(author)
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Barlow, GrahamStanford Univ, Sch Med, Dept Med, Stanford, CA USA.
(author)
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Falk, Ben A.Benaroya Res Inst, Matrix Biol Program, Seattle, WA USA.
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Medina, Carlos O.Stanford Univ, Sch Med, Dept Med, Stanford, CA USA.
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Hargil, AvivStanford Univ, Sch Med, Dept Med, Stanford, CA USA.
(author)
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Zihsler, SvenjaStanford Univ, Sch Med, Dept Med, Stanford, CA USA.
(author)
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Vlodavsky, IsraelTechnion, Technion Integrated Canc Ctr, Haifa, Israel.
(author)
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Li, Jin-PingUppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi(Swepub:uu)jinpili
(author)
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Perez-Cruz, MagdielStanford Univ, Sch Med, Dept Med, Stanford, CA USA.
(author)
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Tang, Sai-WenStanford Univ, Sch Med, Dept Med, Stanford, CA USA.
(author)
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Meyer, Everett H.Stanford Univ, Sch Med, Dept Med, Stanford, CA USA.
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Wrenshall, Lucile E.Wright State Univ, Boonshoft Sch Med, Dept Neurosci Cell Biol & Physiol, Dayton, OH 45459 USA.
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Lord, James D.Benaroya Res Inst, Translat Res Program, Seattle, WA USA.
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Garcia, K. ChristopherStanford Univ, Sch Med, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA.
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Palmer, Theo D.Stanford Univ, Sch Med, Dept Neurosurg, Stanford, CA USA.
(author)
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Steinman, LawrenceStanford Univ, Sch Med, Dept Neurol & Neurol Sci, Stanford, CA USA.
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Nepom, Gerald T.Immune Tolerance Network, Benaroya Res Inst, Seattle, WA USA.
(author)
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Wight, Thomas N.Benaroya Res Inst, Matrix Biol Program, Seattle, WA USA.
(author)
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Bollyky, Paul L.Stanford Univ, Sch Med, Dept Med, Stanford, CA USA.
(author)
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Kuipers, Hedwich F.Univ Calgary, Cumming Sch Med, Dept Clin Neurosci, Calgary, AB, Canada.;Univ Calgary, Cumming Sch Med, Hotchkiss Brain Inst, Calgary, AB, Canada.;Univ Calgary, Cumming Sch Med, Snyder Inst Chron Dis, Calgary, AB, Canada.;Univ Calgary, Cumming Sch Med, Dept Cell Biol & Anat, Calgary, AB, Canada.
(author)
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Stanford Univ, Sch Med, Dept Med, Stanford, CA USA.Univ Calgary, Cumming Sch Med, Dept Clin Neurosci, Calgary, AB, Canada.;Univ Calgary, Cumming Sch Med, Hotchkiss Brain Inst, Calgary, AB, Canada.;Univ Calgary, Cumming Sch Med, Snyder Inst Chron Dis, Calgary, AB, Canada.
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In:Nature Communications: Springer Nature15:12041-1723
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Martinez, Hunter ...
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Koliesnik, Ievge ...
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Kaber, Gernot
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Reid, Jacqueline ...
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Nagy, Nadine
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Barlow, Graham
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Falk, Ben A.
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Medina, Carlos O ...
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Hargil, Aviv
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Zihsler, Svenja
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Vlodavsky, Israe ...
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Li, Jin-Ping
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Perez-Cruz, Magd ...
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Tang, Sai-Wen
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Meyer, Everett H ...
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Wrenshall, Lucil ...
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Lord, James D.
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Garcia, K. Chris ...
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Palmer, Theo D.
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Steinman, Lawren ...
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Nepom, Gerald T.
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Wight, Thomas N.
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