Dataset Information

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.

SUBMITTER: Jones L

PROVIDER: S-EPMC4976330 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Publications

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 L Ho Wen Qi WQ Ying Sze S Ramakrishna Lakshmi L Srinivasan Kandhadayar G KG Yurieva Marina M Ng Wan Pei WP Subramaniam Sharrada S Hamadee Nur H NH Joseph Sabrina S Dolpady Jayashree J Atarashi Koji K Honda Kenya K Zolezzi Francesca F Poidinger Michael M Lafaille Juan J JJ Curotto de Lafaille Maria A MA

Scientific reports 20160808

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 P ...[more]

PMID: 27499025

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Project description:The gastrointestinal tract contains a complex microbial community. Peyer's patches (PPs) play an important role in inducing mucosal immune responses in the gastrointestinal tract. However, little is known about the effect of commensal microbiota on the host's PPs. Here, we analyzed the phenotypic-to-transcriptome changes in the intestine PPs of specific pathogen-free (SPF) and germ-free (GF) piglets (fed in an environment with and without commensal microbiota, respectively) to elucidate the role of commensal microbiota in host intestine mucosal immunity. Analyses of anatomical and histological characteristics showed that commensal microbiota deficiency led to PP hypoplasia, especially regarding B and T cells. A total of 12,444 mRNAs were expressed in 12 libraries; 2,156 and 425 differentially expressed (DE) mRNAs were detected in the jejunal PP (JPP) and ileal PP (IPP), respectively (SPF vs. GF). The shared DE mRNAs of the JPP and IPP were mainly involved in basic physiological and metabolic processes, while the specific DE mRNAs were enriched in regulating immune cells in the JPP and microbial responses and cellular immunity in the IPP. Commensal microbiota significantly modulated the expression of genes related to B-cell functions, including activation, proliferation, differentiation, apoptosis, receptor signaling, germinal center formation, and IgA isotype class switching, particularly in the JPP. TLR4 pathway-related genes were induced in response to microbial colonization and in LPS/SCFA-treated B cells. We also detected 69 and 21 DE lncRNAs in the JPP and IPP, respectively, and four one-to-one lncRNA-mRNA pairs were identified. These findings might represent key regulatory axes for host intestine mucosal immunity development during microbial colonization. Overall, the findings of this study revealed that commensal microbiota modulated phenotypic characteristics and gene expression in the piglet intestine PPs and underscored the importance of early microbial colonization for host mucosal immunity development.

Dataset Information

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

Publications

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

Similar Datasets

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