RelB Deficiency in Dendritic Cells Protects from Autoimmune Inflammation Due to Spontaneous Accumulation of Tissue T Regulatory Cells
RelB Deficiency in Dendritic Cells Protects from Autoimmune Inflammation Due to Spontaneous Accumulation of Tissue T Regulatory Cells
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DOI：
10.4049/jimmunol.1801530
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发表时间：
2019-11-15
影响因子：
4.4
通讯作者：
Ohnmacht, Caspar
中科院分区：
文献类型：
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作者：
Andreas, Nico;Potthast, Maria;Ohnmacht, Caspar
FoxP(3+)调节性T细胞是众所周知的免疫抑制细胞，存在于各种环境中。在这项研究中，我们提供了C57BL/6小鼠树突状细胞(DC)中relB基因敲除导致FoxP(3+)T调节性T细胞(Tregs)自发和系统积累的证据，部分是以微生物区系反应性Tregs为代价的。NFKB2的缺失并不能完全概括这一表型，表明通过RelB/p52复合体替代的NF-kappa B激活并不是Treg积累的唯一原因。树突状细胞中Re1B的缺失进一步导致口服耐受诱导受损，并在累积的FoxP(3+)Tregs中产生明显的2型免疫偏见，这使人想起组织Treg签名。组织Tregs具有完全的功能，独立于IL-33而扩展，并导致几乎完全依赖Treg对实验性自身免疫性脑脊髓炎的保护。因此，我们提供了明确的证据表明，RelB依赖的通路调节DC在数量和质量上影响Treg生物学的能力，并构成治疗自身免疫性疾病的有吸引力的靶点，但可能面临肠道免疫耐受性下降的风险。
Foxp(3+) regulatory T cells are well-known immune suppressor cells in various settings. In this study, we provide evidence that knockout of the relB gene in dendritic cells (DCs) of C57BL/6 mice results in a spontaneous and systemic accumulation of Foxp(3+) T regulatory T cells (Tregs) partially at the expense of microbiota-reactive Tregs. Deletion of nfkb2 does not fully recapitulate this phenotype, indicating that alternative NF-kappa B activation via the RelB/p52 complex is not solely responsible for Treg accumulation. Deletion of Re1B in DCs further results in an impaired oral tolerance induction and a marked type 2 immune bias among accumulated Foxp(3+) Tregs reminiscent of a tissue Treg signature. Tissue Tregs were fully functional, expanded independently of IL-33, and led to an almost complete Treg-dependent protection from experimental autoimmune encephalomyelitis. Thus, we provide clear evidence that RelB-dependent pathways regulate the capacity of DCs to quantitatively and qualitatively impact on Treg biology and constitute an attractive target for treatment of autoimmune diseases but may come at risk for reduced immune tolerance in the intestinal tract.