An immunologic mode of multigenerational transmission governs a gut Treg setpoint


Deepshika Ramanan, Esen Sefik, Silvia Galvin-Pena, Meng Wu, Liang Yang, Zhen Yang, Aleksandar Kostic, Tatyana Golovkina, Dennis L Kasper, Diane Mathis, and Christophe Benoist. 2020. “An immunologic mode of multigenerational transmission governs a gut Treg setpoint.” Cell, 181, 6, Pp. 1276-1290.


At the species level, immunity depends on the selection and transmission of protective components of the immune system. A microbe-induced population of RORg -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. RORg+ 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. RORg+ Treg proportions negatively correlated with IgA production and coating of gut commensals, traits also subject to maternal transmission, in an immunoglobulin- and RORg+ Treg-dependent manner. We propose a model based on a double-negative feedback loop, vertically transmitted via the entero-mammary axis. This immunologicmode of multi-generational transmission may provide adaptability and modulate the genetic tuning of gut immune responses and inflammatory disease susceptibility.

Last updated on 08/12/2020