Department of Immunology, Harvard Medical School, Boston, MA 02115, USA.
Joslin Diabetes Center and Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA.
Cell. 2020 Jun 11;181(6):1276-1290.e13. doi: 10.1016/j.cell.2020.04.030. Epub 2020 May 12.
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.
在物种水平上，免疫取决于免疫系统保护性成分的选择和传递。微生物诱导的表达 RORγ 的调节性 T 细胞（Treg）群体对于控制肠道炎症至关重要。我们发现了一种非遗传、非表观遗传、非微生物的稳态设定点传递模式。RORγ Treg 比例在近交系小鼠品系之间存在差异，这一特征是在出生后严格的年龄窗口内由母亲传递的，但终生稳定，对许多微生物或细胞扰动具有抗性，然后由雌性进一步传递多代。RORγ Treg 比例与 IgA 产生和肠道共生菌的涂层呈负相关，这些特征也受母体传递的影响，以免疫球蛋白和 RORγ Treg 依赖的方式。我们提出了一个基于双负反馈环的模型，通过肠-乳腺轴垂直传递。这种多代传递的免疫模式可能提供了适应性，并调节了肠道免疫反应和炎症性疾病易感性的遗传调整。
