| Autor: |
Hunter A. Martinez, Ievgen Koliesnik, Gernot Kaber, Jacqueline K. Reid, Nadine Nagy, Graham Barlow, Ben A. Falk, Carlos O. Medina, Aviv Hargil, Svenja Zihsler, Israel Vlodavsky, Jin-Ping Li, Magdiel Pérez-Cruz, Sai-Wen Tang, Everett H. Meyer, Lucile E. Wrenshall, James D. Lord, K. Christopher Garcia, Theo D. Palmer, Lawrence Steinman, Gerald T. Nepom, Thomas N. Wight, Paul L. Bollyky, Hedwich F. Kuipers |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Nature Communications, Vol 15, Iss 1, Pp 1-15 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2041-1723 |
| DOI: |
10.1038/s41467-024-45012-9 |
| Popis: |
Abstract 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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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