An Immunologic Mode of Multigenerational Transmission Governs a Gut Treg Setpoint

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 m...

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Vydáno v:	Cell Ročník 181; číslo 6; s. 1276
Hlavní autoři:	Ramanan, Deepshika, Sefik, Esen, Galván-Peña, Silvia, Wu, Meng, Yang, Liang, Yang, Zhen, Kostic, Aleksandar, Golovkina, Tatyana V, Kasper, Dennis L, Mathis, Diane, Benoist, Christophe
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States 11.06.2020
Témata:	Animals Digestive System - immunology Disease Susceptibility - immunology Female Gastrointestinal Microbiome - immunology Homeostasis - immunology Immunoglobulin A - immunology Inflammation - immunology Male Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Inbred CBA Mice, Inbred NOD Nuclear Receptor Subfamily 1, Group F, Member 3 - immunology T-Lymphocytes, Regulatory - immunology Rorγ entero-mammary axis IgA maternal transmission colonic Tregs Tregs
ISSN:	1097-4172, 1097-4172
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Popis
Shrnutí:	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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1097-4172 1097-4172
DOI:	10.1016/j.cell.2020.04.030