Segmented Filamentous Bacteria Provoke Lung Autoimmunity by Inducing Gut-Lung Axis Th17 Cells Expressing Dual TCRs

C. Pierce Bradley, Fei Teng, Krysta M. Felix, Teruyuki Sano, Debdut Naskar, Katharine E. Block, Haochu Huang, Kenneth S Knox, Dan R. Littman, Hsin-Jung Joyce Wu

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Lung complications are a major cause of rheumatoid arthritis-related mortality. Involvement of gut microbiota in lung diseases by the gut-lung axis has been widely observed, but the underlying mechanism remains mostly unknown. Using an autoimmune arthritis model, we show that a constituent of the gut microbiota, segmented filamentous bacteria (SFB), distantly provoke lung pathology. SFB induce autoantibodies in lung during the pre-arthritic phase, and SFB-dependent lung pathology requires the T helper 17 (Th17) responses. SFB-induced gut Th17 cells are preferentially recruited to lung over spleen due to robust expression in the lung of the Th17 chemoattractant, CCL20. Additionally, we found that in peripheral tissues, SFB selectively expand dual T cell receptor (TCR)-expressing Th17 cells recognizing both an SFB epitope and self-antigen, thus augmenting autoimmunity. This study reveals mechanisms for commensal-mediated gut-lung crosstalk and dual TCR-based autoimmunity. Lung complications significantly contribute to rheumatoid arthritis (RA)-related mortality. Bradley et al. demonstrate that gut microbiota SFB trigger RA-related lung pathology during the pre-arthritic phase by inducing Th17 cells of the gut-lung axis. SFB selectively expand autoimmune, dual TCR-expressing Th17 cells that sense both SFB peptide and self-antigen.

Original languageEnglish (US)
Pages (from-to)697-704.e4
JournalCell Host and Microbe
Volume22
Issue number5
DOIs
StatePublished - Nov 8 2017

Fingerprint

Th17 Cells
Autoimmunity
Bacteria
Lung
T-Cell Antigen Receptor
Arthritis
Rheumatoid Arthritis
Autoantigens
Pathology
Mortality
Chemotactic Factors
Autoantibodies
Lung Diseases
Epitopes
Spleen

Keywords

  • autoimmune
  • dual TCR
  • gut microbiota
  • gut-lung axis
  • rheumatoid arthritis
  • Th17 cells

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology

Cite this

Segmented Filamentous Bacteria Provoke Lung Autoimmunity by Inducing Gut-Lung Axis Th17 Cells Expressing Dual TCRs. / Bradley, C. Pierce; Teng, Fei; Felix, Krysta M.; Sano, Teruyuki; Naskar, Debdut; Block, Katharine E.; Huang, Haochu; Knox, Kenneth S; Littman, Dan R.; Wu, Hsin-Jung Joyce.

In: Cell Host and Microbe, Vol. 22, No. 5, 08.11.2017, p. 697-704.e4.

Research output: Contribution to journalArticle

Bradley, C. Pierce ; Teng, Fei ; Felix, Krysta M. ; Sano, Teruyuki ; Naskar, Debdut ; Block, Katharine E. ; Huang, Haochu ; Knox, Kenneth S ; Littman, Dan R. ; Wu, Hsin-Jung Joyce. / Segmented Filamentous Bacteria Provoke Lung Autoimmunity by Inducing Gut-Lung Axis Th17 Cells Expressing Dual TCRs. In: Cell Host and Microbe. 2017 ; Vol. 22, No. 5. pp. 697-704.e4.
@article{23059b378afb43279c8dd7200fe686bd,
title = "Segmented Filamentous Bacteria Provoke Lung Autoimmunity by Inducing Gut-Lung Axis Th17 Cells Expressing Dual TCRs",
abstract = "Lung complications are a major cause of rheumatoid arthritis-related mortality. Involvement of gut microbiota in lung diseases by the gut-lung axis has been widely observed, but the underlying mechanism remains mostly unknown. Using an autoimmune arthritis model, we show that a constituent of the gut microbiota, segmented filamentous bacteria (SFB), distantly provoke lung pathology. SFB induce autoantibodies in lung during the pre-arthritic phase, and SFB-dependent lung pathology requires the T helper 17 (Th17) responses. SFB-induced gut Th17 cells are preferentially recruited to lung over spleen due to robust expression in the lung of the Th17 chemoattractant, CCL20. Additionally, we found that in peripheral tissues, SFB selectively expand dual T cell receptor (TCR)-expressing Th17 cells recognizing both an SFB epitope and self-antigen, thus augmenting autoimmunity. This study reveals mechanisms for commensal-mediated gut-lung crosstalk and dual TCR-based autoimmunity. Lung complications significantly contribute to rheumatoid arthritis (RA)-related mortality. Bradley et al. demonstrate that gut microbiota SFB trigger RA-related lung pathology during the pre-arthritic phase by inducing Th17 cells of the gut-lung axis. SFB selectively expand autoimmune, dual TCR-expressing Th17 cells that sense both SFB peptide and self-antigen.",
keywords = "autoimmune, dual TCR, gut microbiota, gut-lung axis, rheumatoid arthritis, Th17 cells",
author = "Bradley, {C. Pierce} and Fei Teng and Felix, {Krysta M.} and Teruyuki Sano and Debdut Naskar and Block, {Katharine E.} and Haochu Huang and Knox, {Kenneth S} and Littman, {Dan R.} and Wu, {Hsin-Jung Joyce}",
year = "2017",
month = "11",
day = "8",
doi = "10.1016/j.chom.2017.10.007",
language = "English (US)",
volume = "22",
pages = "697--704.e4",
journal = "Cell Host and Microbe",
issn = "1931-3128",
publisher = "Cell Press",
number = "5",

}

TY - JOUR

T1 - Segmented Filamentous Bacteria Provoke Lung Autoimmunity by Inducing Gut-Lung Axis Th17 Cells Expressing Dual TCRs

AU - Bradley, C. Pierce

AU - Teng, Fei

AU - Felix, Krysta M.

AU - Sano, Teruyuki

AU - Naskar, Debdut

AU - Block, Katharine E.

AU - Huang, Haochu

AU - Knox, Kenneth S

AU - Littman, Dan R.

AU - Wu, Hsin-Jung Joyce

PY - 2017/11/8

Y1 - 2017/11/8

N2 - Lung complications are a major cause of rheumatoid arthritis-related mortality. Involvement of gut microbiota in lung diseases by the gut-lung axis has been widely observed, but the underlying mechanism remains mostly unknown. Using an autoimmune arthritis model, we show that a constituent of the gut microbiota, segmented filamentous bacteria (SFB), distantly provoke lung pathology. SFB induce autoantibodies in lung during the pre-arthritic phase, and SFB-dependent lung pathology requires the T helper 17 (Th17) responses. SFB-induced gut Th17 cells are preferentially recruited to lung over spleen due to robust expression in the lung of the Th17 chemoattractant, CCL20. Additionally, we found that in peripheral tissues, SFB selectively expand dual T cell receptor (TCR)-expressing Th17 cells recognizing both an SFB epitope and self-antigen, thus augmenting autoimmunity. This study reveals mechanisms for commensal-mediated gut-lung crosstalk and dual TCR-based autoimmunity. Lung complications significantly contribute to rheumatoid arthritis (RA)-related mortality. Bradley et al. demonstrate that gut microbiota SFB trigger RA-related lung pathology during the pre-arthritic phase by inducing Th17 cells of the gut-lung axis. SFB selectively expand autoimmune, dual TCR-expressing Th17 cells that sense both SFB peptide and self-antigen.

AB - Lung complications are a major cause of rheumatoid arthritis-related mortality. Involvement of gut microbiota in lung diseases by the gut-lung axis has been widely observed, but the underlying mechanism remains mostly unknown. Using an autoimmune arthritis model, we show that a constituent of the gut microbiota, segmented filamentous bacteria (SFB), distantly provoke lung pathology. SFB induce autoantibodies in lung during the pre-arthritic phase, and SFB-dependent lung pathology requires the T helper 17 (Th17) responses. SFB-induced gut Th17 cells are preferentially recruited to lung over spleen due to robust expression in the lung of the Th17 chemoattractant, CCL20. Additionally, we found that in peripheral tissues, SFB selectively expand dual T cell receptor (TCR)-expressing Th17 cells recognizing both an SFB epitope and self-antigen, thus augmenting autoimmunity. This study reveals mechanisms for commensal-mediated gut-lung crosstalk and dual TCR-based autoimmunity. Lung complications significantly contribute to rheumatoid arthritis (RA)-related mortality. Bradley et al. demonstrate that gut microbiota SFB trigger RA-related lung pathology during the pre-arthritic phase by inducing Th17 cells of the gut-lung axis. SFB selectively expand autoimmune, dual TCR-expressing Th17 cells that sense both SFB peptide and self-antigen.

KW - autoimmune

KW - dual TCR

KW - gut microbiota

KW - gut-lung axis

KW - rheumatoid arthritis

KW - Th17 cells

UR - http://www.scopus.com/inward/record.url?scp=85032742580&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85032742580&partnerID=8YFLogxK

U2 - 10.1016/j.chom.2017.10.007

DO - 10.1016/j.chom.2017.10.007

M3 - Article

C2 - 29120746

AN - SCOPUS:85032742580

VL - 22

SP - 697-704.e4

JO - Cell Host and Microbe

JF - Cell Host and Microbe

SN - 1931-3128

IS - 5

ER -