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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Abstract 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.
AbstractList 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.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.
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.
Author Yang, Zhen
Sefik, Esen
Kasper, Dennis L
Benoist, Christophe
Mathis, Diane
Ramanan, Deepshika
Yang, Liang
Kostic, Aleksandar
Golovkina, Tatyana V
Galván-Peña, Silvia
Wu, Meng
Author_xml – sequence: 1
  givenname: Deepshika
  surname: Ramanan
  fullname: Ramanan, Deepshika
  organization: Department of Immunology, Harvard Medical School, Boston, MA 02115, USA
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  givenname: Esen
  surname: Sefik
  fullname: Sefik, Esen
  organization: Department of Immunology, Harvard Medical School, Boston, MA 02115, USA
– sequence: 3
  givenname: Silvia
  surname: Galván-Peña
  fullname: Galván-Peña, Silvia
  organization: Department of Immunology, Harvard Medical School, Boston, MA 02115, USA
– sequence: 4
  givenname: Meng
  surname: Wu
  fullname: Wu, Meng
  organization: Department of Immunology, Harvard Medical School, Boston, MA 02115, USA
– sequence: 5
  givenname: Liang
  surname: Yang
  fullname: Yang, Liang
  organization: Department of Immunology, Harvard Medical School, Boston, MA 02115, USA
– sequence: 6
  givenname: Zhen
  surname: Yang
  fullname: Yang, Zhen
  organization: Joslin Diabetes Center and Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA
– sequence: 7
  givenname: Aleksandar
  surname: Kostic
  fullname: Kostic, Aleksandar
  organization: Joslin Diabetes Center and Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA
– sequence: 8
  givenname: Tatyana V
  surname: Golovkina
  fullname: Golovkina, Tatyana V
  organization: Department of Microbiology, Committee on Microbiology and Committee on Immunology, University of Chicago, Chicago, IL 60637, USA
– sequence: 9
  givenname: Dennis L
  surname: Kasper
  fullname: Kasper, Dennis L
  organization: Department of Immunology, Harvard Medical School, Boston, MA 02115, USA
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  surname: Mathis
  fullname: Mathis, Diane
  email: cbdm@hms.harvard.edu
  organization: Department of Immunology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: cbdm@hms.harvard.edu
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  surname: Benoist
  fullname: Benoist, Christophe
  email: cbdm@hms.harvard.edu
  organization: Department of Immunology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: cbdm@hms.harvard.edu
BackLink https://www.ncbi.nlm.nih.gov/pubmed/32402238$$D View this record in MEDLINE/PubMed
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Keywords Rorγ
entero-mammary axis
IgA
maternal transmission
colonic Tregs
Tregs
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32497500 - Cell. 2020 Jun 11;181(6):1202-1204
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SubjectTerms Animals
Digestive System - immunology
Disease Susceptibility - immunology
Female
Gastrointestinal Microbiome - immunology
Homeostasis - immunology
Immunoglobulin A - immunology
Inflammation - immunology
Male
Mice
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Mice, Inbred C57BL
Mice, Inbred CBA
Mice, Inbred NOD
Nuclear Receptor Subfamily 1, Group F, Member 3 - immunology
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Title An Immunologic Mode of Multigenerational Transmission Governs a Gut Treg Setpoint
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