Koga Marianna M, Engel Adrien, Pigni Matteo, Lavanchy Christine, Stevanin Mathias, Laversenne Vanessa, Schneider Bernard L, Acha-Orbea Hans
Department of Biochemistry, Center of Immunity and Infection Lausanne, University of Lausanne, Lausanne, Switzerland.
Brain Mind Institute, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Front Immunol. 2021 Feb 17;12:607315. doi: 10.3389/fimmu.2021.607315. eCollection 2021.
Dendritic cells (DCs) are professional antigen-presenting cells involved in the initiation of immune responses. We generated a tolerogenic DC (tolDC) line that constitutively secretes interleukin-10 (IL10-DCs), expressed lower levels of co-stimulatory and MHCII molecules upon stimulation, and induced antigen-specific proliferation of T cells. Vaccination with IL10-DCs combined with another tolDC line that secretes IL-35, reduced antigen-specific local inflammation in a delayed-type hypersensitivity assay independently on regulatory T cell differentiation. In an autoimmune model of rheumatoid arthritis, vaccination with the combined tolDCs after the onset of the disease impaired disease development and promoted recovery of mice. After stable memory was established, the tolDCs promoted CD4 downregulation and induced lymphocyte activation gene 3 (LAG-3) expression in reactivated memory T cells, reducing T cell activation. Taken together, our findings indicate the benefits of combining anti-inflammatory cytokines in an antigen-specific context to treat excessive inflammation when memory is already established.
树突状细胞（DCs）是参与免疫反应起始的专职抗原呈递细胞。我们构建了一种组成性分泌白细胞介素-10的耐受性DC（tolDC）系（IL10-DCs），其在受到刺激时共刺激分子和MHCII分子表达水平较低，并能诱导T细胞的抗原特异性增殖。将IL10-DCs与另一种分泌IL-35的tolDC系联合接种疫苗，在迟发型超敏反应试验中可独立于调节性T细胞分化减少抗原特异性局部炎症。在类风湿性关节炎的自身免疫模型中，疾病发作后用联合tolDCs接种疫苗可损害疾病发展并促进小鼠恢复。在建立稳定记忆后，tolDCs促进再激活的记忆T细胞中CD4下调并诱导淋巴细胞激活基因3（LAG-3）表达，从而降低T细胞活化。综上所述，我们的研究结果表明，在已经建立记忆时，在抗原特异性背景下联合抗炎细胞因子治疗过度炎症具有益处。
