Date: Monday, November 6, 2017
Session Title: T Cell Biology and Targets in Autoimmune Disease Poster I
Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose: Helper T cell subsets including Th17 cells and regulatory T (Treg) cells play a role in the adaptive immune response. RORC and Foxp3 are master regulators of Th17 and Treg cells, respectively, and the gene expressions are suggested to be unstable in vivo. Th17 cells re-differentiated into unconventional Th1 cells (Th17/Th1 type cell conversion) and Treg cells converted into Th17 cells (Treg/Th17 type cell conversion) in experimental transplantation models. The converting T cells were more pathogenic in the lesions than conventional cells.
Recently, researchers found that gut microbes had close relationships with Th17 cell and Treg cell induction in the animals and humans. Intestinal colonization of segmented filamentous bacteria and short chain fatty acid (SCFA)-producing bacteria induce Th17 and Treg cells, respectively, and modulates the systemic inflammation of diseased mice. SCFAs in the intestine are important not only as Treg cell differentiators but also as major energy sources for the colonic wall.
We have reported characteristic features of gut microbiota and Th17/Th1 type T cell conversion shown in patients with Behcet’s disease (PLoS One 2016;11:e0153746, Clin Rheumatol 2016;35:1857–63). The metagenomics suggested an intestinal depletion of SCFAs in the patients. We then analyzed fecal metagenomic and T cell gene expression data of patients with relapsing polychondritis (RP).
Methods: We explored fecal microbiota of 10 patients with RP and 16 normal individuals (NI) by sequencing of 16S rRNA gene. We calculated relative abundance of bacterial taxa using QIIME software. We stimulated peripheral blood mononuclear cells of 9 RP patients and 10 NI with lectin and measured Th17/Treg cell-related gene expressions.
Results: The sequencing data showed that the family Ruminococcaseae and the species Faecalibacterium prausnitzii increased significantly in RP patients compared with NI. The species is one of the major butyrate (a SCFA)-producing bacteria of the human intestine. RP T cell gene expression analyses revealed that Foxp3 gene expression increased remarkably in RP patients compared with NI. We observed that RORC gene expression increased significantly with antigen stimulation in RP patients. Thus, RP T cells were suggested to demonstrate Treg/Th17 type cell conversion in the in vitro assay.
Conclusion: We consider that RP-specific gut microbes with the increased butyrate production may induce and maintain Treg cells in the intestine. The gut differentiated RP Treg cells may associated with subsequent inflammatory processes and their conversion into pathogenic Th17 cells in the absence of butyrate.
To cite this abstract in AMA style:Shimizu J, Kubota T, Suzuki N. An Abundance of Butyrate-Producing Bacterium in the Intestine and Increased Foxp3 Gene Expression of T Cells in Patients with Relapsing Polychondritis [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/an-abundance-of-butyrate-producing-bacterium-in-the-intestine-and-increased-foxp3-gene-expression-of-t-cells-in-patients-with-relapsing-polychondritis/. Accessed July 11, 2020.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/an-abundance-of-butyrate-producing-bacterium-in-the-intestine-and-increased-foxp3-gene-expression-of-t-cells-in-patients-with-relapsing-polychondritis/