Proceedings of the National Academy of Sciences · 2021 · 51 citations · 40 references
Life SciencesImmunologyNeuroscienceAutoimmunityImmunoregulationNeuroimmunologyAutoimmune Disease PathogenesisAutoimmune DiseasesAutoimmune Neurological DisordersMultiple SclerosisNeuroinflammationRegulatory T CellsExperimental Autoimmune EncephalomyelitisImmune-mediated PathogenesisMultiple Sclerosis ImmunopathogenesisMultiple Sclerosis ImmunopathologyMultiple Sclerosis PathologyMultiple Sclerosis TherapyPathogenic EffectsTissue-restricted Gene Expression
Regulatory T cells are key in limiting autoimmune disease severity, but their anatomical location and timing of suppression remain unclear. In a mouse MS model, Treg cells suppress disease within the CNS during established disease via TNFR2, and loss of TNFR2 worsens symptoms, indicating TNFR2 as a therapeutic target.
Significance Regulatory T (Treg) cells have been highlighted for their central function in limiting the severity of autoimmune diseases such as multiple sclerosis (MS). To date, the anatomical location and timing of this Treg cell–mediated suppression are unknown. In this report, in a mouse model of MS, we demonstrate that Treg cells inhibit the pathogenic process directly in the central nervous system during established disease, rather than in the presymptomatic phase. This protective function requires the surface expression of TNF receptor 2 by Treg cells, as its genetic ablation or antibody-mediated blockade worsens disease symptoms. Our data reveal a unique function of Treg cells in autoimmunity and highlight TNFR2 as a promising therapeutic target.
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