At the species level, immunity depends on the selection and transmission of protective components of the immune system. A microbe-induced population of RORγ-expressing regulatory T cells (Tregs) is essential in controlling gut inflammation. We uncovered a non-genetic, non-epigenetic, non-microbial mode of transmission of their homeostatic setpoint. RORγ⁺ Treg proportions varied between inbred mouse strains, a trait transmitted by the mother during a tight age window after birth but stable for life, resistant to many microbial or cellular perturbations, then further transferred by females for multiple generations. RORγ⁺ Treg proportions negatively correlated with IgA production and coating of gut commensals, traits also subject to maternal transmission, in an immunoglobulin- and RORγ⁺ Treg-dependent manner. We propose a model based on a double-negative feedback loop, vertically transmitted via the entero-mammary axis. This immunologic mode of multi-generational transmission may provide adaptability and modulate the genetic tuning of gut immune responses and inflammatory disease susceptibility.

在物种层面，免疫力取决于免疫系统保护成分的选择和传播。微生物诱导的表达RORγ的调节性T细胞（Tregs）群体在控制肠道炎症中至关重要。我们发现了其稳态设定值的非遗传，非表观遗传，非微生物传播方式。RORγ ⁺ Treg比例在近交小鼠品系之间有所不同，这是母亲在出生后的紧缩年龄窗口内传播的特征，但终生稳定，可抵抗多种微生物或细胞干扰，然后由雌性进一步传代数代。RORγ ⁺ Treg比例与免疫球蛋白和RORγ呈负相关，与IgA的产生和肠膜的包被呈负相关，性状也易受母体传播。⁺ Treg依赖方式。我们提出了一个基于双负反馈回路的模型，该模型通过肠乳腺轴垂直传输。这种多代传播的免疫学模式可以提供适应性，并调节肠道免疫反应和炎症性疾病易感性的基因调节。