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Chen, H.H.* ; Tyystjärvi, S.* ; Ruiz Navarro, D.* ; Kant, R.* ; Groll, T.* ; Wagner, I.* ; Domínguez Moreno, H.* ; Bonafonte Pardás, I. ; Öllinger, R.* ; Afzali, A.M.* ; Heink, S.* ; Richter, L.C.* ; Sie, C.* ; Lepennetier, G.* ; Seeholzer, L.* ; Steiger, K.* ; Merkler, D.* ; Rad, R.* ; Schotta, G.* ; Schubert, B. ; Muschaweckh, A.* ; Korn, T.*

CD38 endows local antigen-specific Treg cells with stress resilience for control of compartmentalized CNS inflammation.

Nat. Immunol. 27, 516-529 (2026)
Verlagsversion Forschungsdaten DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
Foxp3-expressing regulatory T (Treg) cells protect against systemic autoimmunity. However, little is known about the significance of Treg cells in inflammation-experienced tissues. Here, we use an experimental autoimmune encephalomyelitis model and show that Treg cells accumulate and persist in the central nervous system (CNS) long after the resolution of the bulk of the inflammatory infiltrate. CNS-specific depletion of postinflammatory Treg cells, but not systemic depletion of Treg cells, results in autoimmune inflammatory flares in the CNS by residual local effector T cells. Expression of the NAD-consuming ectoenzyme CD38 is crucial for the functional adaptation of postinflammatory CNS Treg cells to a stressful microenvironment, in which access to interleukin-2 (IL-2) is limited. CD38 counteracts ADP-ribosylation of the IL-2 receptor and thus maintains its high sensitivity to IL-2. This fully functional high-affinity IL-2 receptor prevents the loss of tissue-resident antigen-specific Treg cells. These 'stress-tolerant' CNS Treg cells impede the collapse of immune homeostasis in the CNS once acute inflammation is controlled.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Experimental Autoimmune Encephalomyelitis ; Inflammation ; Cd38 ; Immune System ; Effector ; Central Nervous System ; Homeostasis ; Cytotoxic T Cell; Nicotinamide Adenine-dinucleotide; Adp-ribosylation; Tissue; Differentiation; Lymphocytes; Expression; Disease; Repair; Foxp3; Irf4
ISSN (print) / ISBN 1529-2908
e-ISSN 1529-2916
Zeitschrift Nature Immunology
Quellenangaben Band: 27, Heft: 3, Seiten: 516-529 Artikelnummer: , Supplement: ,
Verlag Nature Publishing Group
Verlagsort Heidelberger Platz 3, Berlin, 14197, Germany
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Computational Biology (ICB)
Förderungen Gemeinntzige Hertie-Stiftung (Hertie Foundation)
Deutsche Forschungsgemeinschaft (German Research Foundation)