| First Author | Ramanan D | Year | 2020 |
| Journal | Cell | Volume | 181 |
| Issue | 6 | Pages | 1276-1290.e13 |
| PubMed ID | 32402238 | Mgi Jnum | J:300647 |
| Mgi Id | MGI:6442218 | Doi | 10.1016/j.cell.2020.04.030 |
| Citation | Ramanan D, et al. (2020) An Immunologic Mode of Multigenerational Transmission Governs a Gut Treg Setpoint. Cell 181(6):1276-1290.e13 |
| abstractText | At the species level, immunity depends on the selection and transmission of protective components of the immune system. A microbe-induced population of RORgamma-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. RORgamma(+) 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. RORgamma(+) Treg proportions negatively correlated with IgA production and coating of gut commensals, traits also subject to maternal transmission, in an immunoglobulin- and RORgamma(+) 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. |
