Trained immunity is the ability of the innate immune system to form immune memory responses to provide support the formation of appropriate adaptive responses. Allergic airways disease (AAD) is a maladapted immune response to allergens, initiated and maintained by the type 2 (T2) inflammatory pathway. It is predicated by the elaboration of cytokines IL-4 and IL-13 and follows activation of the STAT6 transcription factor. To investigate the role of trained immunity in mucosal immune responses following neonatal vaccination with the STAT6 inhibitory peptide (STAT6-IP), in preventing the development of ragweed-induced AAD. We demonstrate that transfer of CD4+ T cells or dendritic cells (DC) from STAT6-IP vaccinated wild-type BALB/c mice to naïve mice, that were subsequently chronically exposed to sensitizing doses of ragweed allergen, is sufficient to prevent development of T2 responses in recipients. Our results demonstrate significant reductions in; airways hyperresponsiveness (AHR); ragweed-specific IgE; pulmonary inflammation; T2 cytokines; and inflammatory gene expressions in recipient mice. Expression of IDO, TGFβ and T regulatory cells were all significantly increased. Anti-TGFβ treatment during the ragweed sensitization phase re-constituted the pro-inflammatory T2 immune response. We show that tolerance can be attained via DC trained in the STAT6-IP-mediated tolerant milieu. This effect is not restricted to a particular allergen and does not require antigen-mediated T cell activation prior to transfer. Adoptive transfer experiments suggest that STAT6-IP treatment trains dendritic and cells to mediate tolerant immunity to chronic ragweed exposure in the airways. This indicates that early transient STAT6-inhibition constitutes an effective immunomodulatory airways allergy preventative strategy.

中文翻译：

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体内基于肽的STAT6抑制作用诱导的免疫训练可防止豚鼠过敏

训练后的免疫力是先天免疫系统形成免疫记忆反应以提供适当适应性反应支持的能力。过敏性气道疾病（AAD）是对过敏原的不良适应性免疫反应，由2型（T2）炎症途径引发和维持。它由细胞因子IL-4和IL-13的合成来预测，并跟随STAT6转录因子的激活。为了研究在用STAT6抑制肽（STAT6-IP）进行新生儿疫苗接种后，粘膜免疫反应中受过训练的免疫在预防豚草诱导的AAD发生中的作用。我们证明了CD4 + T细胞或树突状细胞（DC）从STAT6-IP疫苗接种的野生型BALB / c小鼠转移至幼稚的小鼠，这些小鼠随后长期暴露于致敏剂量的豚草变应原，足以防止在收件人中产生T2响应。我们的结果表明显着降低；气道高反应性（AHR）；豚草特异性IgE；肺部炎症；T2细胞因子；受体小鼠体内的炎症和炎症基因表达。IDO，TGFβ和T调节细胞的表达均显着增加。豚草致敏期的抗TGFβ治疗重建了促炎性T2免疫应答。我们表明，可以通过在STAT6-IP介导的耐受环境中训练的DC来获得耐受性。该作用不限于特定的变应原，并且在转移之前不需要抗原介导的T细胞活化。过继转移实验表明，STAT6-IP处理可训练树突状细胞和细胞介导对气道中慢性豚草暴露的耐受性免疫力。