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...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Cell Jg. 181; H. 6; S. 1276
Hauptverfasser: 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
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 11.06.2020
Schlagworte:
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
Online-Zugang:Weitere Angaben
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung: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.
Bibliographie: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