期刊
CELL
卷 181, 期 6, 页码 1276-+出版社
CELL PRESS
DOI: 10.1016/j.cell.2020.04.030
关键词
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资金
- NIH, United States [AI125603, AI051530]
- UCB
- Evelo Biosciences
- Damon Runyon Cancer Research Foundation, United States [DRG 2300-17]
- EMBO, Germany [ALTF 547-2019]
At the species level, immunity depends on the selection and transmission of protective components of the immune system. A microbe-induced population of ROR gamma-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. ROR gamma(+) 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. ROR gamma(+) Treg proportions negatively correlated with IgA production and coating of gut commensals, traits also subject to maternal transmission, in an immunoglobulin- and ROR gamma(+) 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.
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