A subpopulation of high IL-21-producing CD4+ T cells in Peyer's Patches is induced by the microbiota and regulates germinal centers

Leigh Jones, Wen Qi Ho, Sze Ying, Lakshmi Ramakrishna, Kandhadayar G. Srinivasan, Marina Yurieva, Wan Pei Ng, Sharrada Subramaniam, Nur H. Hamadee, Sabrina Joseph, Jayashree Dolpady, Koji Atarashi, Kenya Honda, Francesca Zolezzi, Michael Poidinger, Juan J. Lafaille, Maria A. Curotto De Lafaille

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

The production of IL-21 by T follicular helper (Tfh) cells is vital in driving the germinal centre reaction and high affinity antibody formation. However, the degree of Tfh cell heterogeneity and function is not fully understood. We used a novel IL-21eGFP reporter mouse strain to analyze the diversity and role of Tfh cells. Through the analysis of GFP expression in lymphoid organs of IL-21eGFP mice, we identified a subpopulation of GFP+, high IL-21 producing Tfh cells present only in Peyer's Patches. GFP+ Tfh cells were found to be polyclonal and related to GFP- Tfh cells of Peyer's Patches in TCR repertoire composition and overall gene expression. Studies on the mechanisms of induction of GFP+ Tfh cells demonstrated that they required the intestinal microbiota and a diverse repertoire of CD4+ T cells and B cells. Importantly, ablation of GFP+ cells resulted in a reduced frequency of Peyer's Patches IgG1 and germinal center B cells in addition to small but significant shifts in gut microbiome composition. Our work highlights the diversity among IL-21 producing CD4+ Tfh cells, and the interrelationship between the intestinal bacteria and Tfh cell responses in the gut.

Original languageEnglish
Article number30784
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - 2016 Aug 8

Fingerprint

Peyer's Patches
Germinal Center
Microbiota
Helper-Inducer T-Lymphocytes
T-Lymphocytes
B-Lymphocytes
interleukin-21
Antibody Formation
Immunoglobulin G
Bacteria
Gene Expression

ASJC Scopus subject areas

  • General

Cite this

Jones, L., Ho, W. Q., Ying, S., Ramakrishna, L., Srinivasan, K. G., Yurieva, M., ... Curotto De Lafaille, M. A. (2016). A subpopulation of high IL-21-producing CD4+ T cells in Peyer's Patches is induced by the microbiota and regulates germinal centers. Scientific Reports, 6, [30784]. https://doi.org/10.1038/srep30784

A subpopulation of high IL-21-producing CD4+ T cells in Peyer's Patches is induced by the microbiota and regulates germinal centers. / Jones, Leigh; Ho, Wen Qi; Ying, Sze; Ramakrishna, Lakshmi; Srinivasan, Kandhadayar G.; Yurieva, Marina; Ng, Wan Pei; Subramaniam, Sharrada; Hamadee, Nur H.; Joseph, Sabrina; Dolpady, Jayashree; Atarashi, Koji; Honda, Kenya; Zolezzi, Francesca; Poidinger, Michael; Lafaille, Juan J.; Curotto De Lafaille, Maria A.

In: Scientific Reports, Vol. 6, 30784, 08.08.2016.

Research output: Contribution to journalArticle

Jones, L, Ho, WQ, Ying, S, Ramakrishna, L, Srinivasan, KG, Yurieva, M, Ng, WP, Subramaniam, S, Hamadee, NH, Joseph, S, Dolpady, J, Atarashi, K, Honda, K, Zolezzi, F, Poidinger, M, Lafaille, JJ & Curotto De Lafaille, MA 2016, 'A subpopulation of high IL-21-producing CD4+ T cells in Peyer's Patches is induced by the microbiota and regulates germinal centers', Scientific Reports, vol. 6, 30784. https://doi.org/10.1038/srep30784
Jones, Leigh ; Ho, Wen Qi ; Ying, Sze ; Ramakrishna, Lakshmi ; Srinivasan, Kandhadayar G. ; Yurieva, Marina ; Ng, Wan Pei ; Subramaniam, Sharrada ; Hamadee, Nur H. ; Joseph, Sabrina ; Dolpady, Jayashree ; Atarashi, Koji ; Honda, Kenya ; Zolezzi, Francesca ; Poidinger, Michael ; Lafaille, Juan J. ; Curotto De Lafaille, Maria A. / A subpopulation of high IL-21-producing CD4+ T cells in Peyer's Patches is induced by the microbiota and regulates germinal centers. In: Scientific Reports. 2016 ; Vol. 6.
@article{cdf5c0f6b9584fd7b03a3ca27f671b45,
title = "A subpopulation of high IL-21-producing CD4+ T cells in Peyer's Patches is induced by the microbiota and regulates germinal centers",
abstract = "The production of IL-21 by T follicular helper (Tfh) cells is vital in driving the germinal centre reaction and high affinity antibody formation. However, the degree of Tfh cell heterogeneity and function is not fully understood. We used a novel IL-21eGFP reporter mouse strain to analyze the diversity and role of Tfh cells. Through the analysis of GFP expression in lymphoid organs of IL-21eGFP mice, we identified a subpopulation of GFP+, high IL-21 producing Tfh cells present only in Peyer's Patches. GFP+ Tfh cells were found to be polyclonal and related to GFP- Tfh cells of Peyer's Patches in TCR repertoire composition and overall gene expression. Studies on the mechanisms of induction of GFP+ Tfh cells demonstrated that they required the intestinal microbiota and a diverse repertoire of CD4+ T cells and B cells. Importantly, ablation of GFP+ cells resulted in a reduced frequency of Peyer's Patches IgG1 and germinal center B cells in addition to small but significant shifts in gut microbiome composition. Our work highlights the diversity among IL-21 producing CD4+ Tfh cells, and the interrelationship between the intestinal bacteria and Tfh cell responses in the gut.",
author = "Leigh Jones and Ho, {Wen Qi} and Sze Ying and Lakshmi Ramakrishna and Srinivasan, {Kandhadayar G.} and Marina Yurieva and Ng, {Wan Pei} and Sharrada Subramaniam and Hamadee, {Nur H.} and Sabrina Joseph and Jayashree Dolpady and Koji Atarashi and Kenya Honda and Francesca Zolezzi and Michael Poidinger and Lafaille, {Juan J.} and {Curotto De Lafaille}, {Maria A.}",
year = "2016",
month = "8",
day = "8",
doi = "10.1038/srep30784",
language = "English",
volume = "6",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - A subpopulation of high IL-21-producing CD4+ T cells in Peyer's Patches is induced by the microbiota and regulates germinal centers

AU - Jones, Leigh

AU - Ho, Wen Qi

AU - Ying, Sze

AU - Ramakrishna, Lakshmi

AU - Srinivasan, Kandhadayar G.

AU - Yurieva, Marina

AU - Ng, Wan Pei

AU - Subramaniam, Sharrada

AU - Hamadee, Nur H.

AU - Joseph, Sabrina

AU - Dolpady, Jayashree

AU - Atarashi, Koji

AU - Honda, Kenya

AU - Zolezzi, Francesca

AU - Poidinger, Michael

AU - Lafaille, Juan J.

AU - Curotto De Lafaille, Maria A.

PY - 2016/8/8

Y1 - 2016/8/8

N2 - The production of IL-21 by T follicular helper (Tfh) cells is vital in driving the germinal centre reaction and high affinity antibody formation. However, the degree of Tfh cell heterogeneity and function is not fully understood. We used a novel IL-21eGFP reporter mouse strain to analyze the diversity and role of Tfh cells. Through the analysis of GFP expression in lymphoid organs of IL-21eGFP mice, we identified a subpopulation of GFP+, high IL-21 producing Tfh cells present only in Peyer's Patches. GFP+ Tfh cells were found to be polyclonal and related to GFP- Tfh cells of Peyer's Patches in TCR repertoire composition and overall gene expression. Studies on the mechanisms of induction of GFP+ Tfh cells demonstrated that they required the intestinal microbiota and a diverse repertoire of CD4+ T cells and B cells. Importantly, ablation of GFP+ cells resulted in a reduced frequency of Peyer's Patches IgG1 and germinal center B cells in addition to small but significant shifts in gut microbiome composition. Our work highlights the diversity among IL-21 producing CD4+ Tfh cells, and the interrelationship between the intestinal bacteria and Tfh cell responses in the gut.

AB - The production of IL-21 by T follicular helper (Tfh) cells is vital in driving the germinal centre reaction and high affinity antibody formation. However, the degree of Tfh cell heterogeneity and function is not fully understood. We used a novel IL-21eGFP reporter mouse strain to analyze the diversity and role of Tfh cells. Through the analysis of GFP expression in lymphoid organs of IL-21eGFP mice, we identified a subpopulation of GFP+, high IL-21 producing Tfh cells present only in Peyer's Patches. GFP+ Tfh cells were found to be polyclonal and related to GFP- Tfh cells of Peyer's Patches in TCR repertoire composition and overall gene expression. Studies on the mechanisms of induction of GFP+ Tfh cells demonstrated that they required the intestinal microbiota and a diverse repertoire of CD4+ T cells and B cells. Importantly, ablation of GFP+ cells resulted in a reduced frequency of Peyer's Patches IgG1 and germinal center B cells in addition to small but significant shifts in gut microbiome composition. Our work highlights the diversity among IL-21 producing CD4+ Tfh cells, and the interrelationship between the intestinal bacteria and Tfh cell responses in the gut.

UR - http://www.scopus.com/inward/record.url?scp=84981218340&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84981218340&partnerID=8YFLogxK

U2 - 10.1038/srep30784

DO - 10.1038/srep30784

M3 - Article

C2 - 27499025

AN - SCOPUS:84981218340

VL - 6

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 30784

ER -