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<p>Foxp3-expressing regulatory T (T<sub>reg</sub>) cells protect against systemic autoimmunity. However, little is known about the significance of T<sub>reg</sub> cells in inflammation-experienced tissues. Here, we use an experimental autoimmune encephalomyelitis model and show that T<sub>reg</sub> 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 T<sub>reg</sub> cells, but not systemic depletion of T<sub>reg</sub> 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 T<sub>reg</sub> 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 T<sub>reg</sub> cells. These ‘stress-tolerant’ CNS T<sub>reg</sub> cells impede the collapse of immune homeostasis in the CNS once acute inflammation is controlled.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月29日

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  • Hsin-Hsiang Chen,
  • Sofia Tyystjärvi,
  • Diego Ruiz Navarro,
  • Ravi Kant,
  • Tanja Groll,
  • Ingrid Wagner,
  • Helena Domínguez Moreno,
  • Irene Bonafonte-Pardàs,
  • Rupert Öllinger,
  • Ali Maisam Afzali,
  • Sylvia Heink,
  • Lisa Charlotte Richter,
  • Christopher Sie,
  • Gildas Lepennetier,
  • Lea Seeholzer,
  • Katja Steiger,
  • Doron Merkler,
  • Roland Rad,
  • Gunnar Schotta,
  • Benjamin Schubert,
  • Andreas Muschaweckh,
  • Thomas Korn

摘要

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.