Intestinal integrity is maintained by balanced numbers of CD103⁺ Dendritic cells (DCs), which generate peripherally induced regulatory T cells (iTregs). We have developed a mouse model where DC-specific constitutive CD40 signals caused a strong reduction of CD103⁺ DCs in the lamina propria (LP) and intestinal lymph nodes (LN). As a consequence, also iTregs were strongly reduced and transgenic mice on the C57Bl/6-background (B6) developed fatal colitis. Here we describe that transgenic mice on a pure Balb/c-background (B/c) do not show any pathologies, while transgenic C57Bl/6 x Balb/c (F1) mice develop weak colon inflammation, without fatal colitis. This graded pathology correlated with the effects of CD40-signalling on DCs in each background, with striking loss of CD103⁺ DCs in B6, but reduced in F1 and diminished in B/c background. We further show direct correlation of CD103⁺ DC-numbers with numbers of iTregs, the frequencies of which behave correspondingly. Striking effects on B6-DCs reflected robust loss of surface MHCII, known to be crucial for iTreg induction. Furthermore, elevated levels of IL-23 together with IL-1, found only in B6 mice, support generation of intestinal IFN-γ⁺IL-17⁺ Th17 cells and IFN-γ⁺ Th1 cells, responsible for onset of disease. Together, this demonstrates a novel aspect of colitis-control, depending on genetic background. Moreover, strain-specific environmental sensing might alter the CD103⁺ DC/iTreg-axis to tip intestinal homeostatic balance to pathology.

平衡数量的CD103 ⁺树突状细胞（DC）可以维持肠的完整性，而CD103 ⁺树突状细胞可产生外周诱导的调节性T细胞（iTregs）。我们已经开发了一种小鼠模型，其中DC特异性组成型CD40信号导致固有层（LP）和肠淋巴结（LN）中CD103 ⁺ DC的强烈减少。结果，iTregs也大大降低，并且在C57Bl / 6-背景（B6）上的转基因小鼠发展为致命性结肠炎。在这里，我们描述了纯Balb / c背景（B / c）上的转基因小鼠未显示任何病理，而转基因C57Bl / 6 x Balb / c（F1）小鼠则表现出弱的结肠炎症，而没有致命的结肠炎。这种病理分级与每个背景中DC信号传递对CD40的影响有关，并伴有CD103 ^+的明显丢失。B6中的DC，但F1中的DC减小，而B / c背景中的DC减小。我们进一步展示了CD103 ⁺ DC数与iTreg数的直接相关性，其频率相应地表现。对B6-DC的打击作用反映了表面MHCII的强烈损失，已知这对iTreg诱导至关重要。此外，仅在B6小鼠中发现的IL-23和IL-1水平升高，支持了引起疾病发作的肠道IFN-γ ⁺ IL-17 ⁺ Th17细胞和IFN-γ ⁺ Th1细胞的产生。总之，这证明了结肠炎控制的一个新方面，具体取决于遗传背景。此外，因应变而异的环境感应可能会改变CD103 ⁺ DC / iTreg轴可提示肠道稳态与病理平衡。