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IL-1β–driven osteoclastogenic Tregs accelerate bone erosion in arthritis

ABSTRACT: IL-1β–driven osteoclastogenic Tregs accelerate bone erosion in arthritis

PROVIDER: PRJNA759793 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR15698693.fastq.gz	Fastqsanger.gz
	SRR15698693_1.fastq.gz	Fastqsanger.gz
	SRR15698693_2.fastq.gz	Fastqsanger.gz
	SRR15698694.fastq.gz	Fastqsanger.gz
	SRR15698694_1.fastq.gz	Fastqsanger.gz

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IL-1β–driven osteoclastogenic Tregs accelerate bone erosion in arthritis

Project description:Purpose: The goal of this study is to evaluate Il1rn-/- Tregs features by bulk RNA sequencing (RNA-seq) of Tregs from WT and Il1rn-/- lymph nodes. Methods: mRNA profiles of isolated CD4+Foxp3eGFP+ from lymph nodes of three 35-day-old wild-type (WT) and three Il1rn-/- mice were generated by deep sequencing. RNA was extracted from sorted cells (5X10^4) using a Qiagen RNeasy Micro Kit. RNA-seq was performed using the Smart-Seq2 platform. Smart-Seq2 libraries were prepared by the Broad Technology Labs and sequenced by the Joint Biology Consortium– associated Broad Genomics Platform. Transcripts were quantified by the Broad computational pipeline using Cuffquant version 2.2.1. Results: WT and Il1rn-/- Tregs showed similar expression of multiple genes associated with suppressor function, including Foxp3, Il2ra, Il7r, and Ebi3 (a component of the suppressive cytokine IL-35), and transcription factors including E_o_m_e_s_, Tbx21 (encoding Tbet), and Irf4. Tregs from WT and Il1rn-/- _mice showed similar expression of genes encoding molecules involved in Treg localization and trafficking, including CXCR6, CXCR3, and CCR10. However, gene set enrichment analysis (GSEA) identified enhanced expression of genes encoding proteins involved in fatty acid metabolism (for example, NTHL1 and GABARAPL1) in Il1rn-/- Tregs and oxidative phosphorylation (OxPhos; for example, ATP5H and NDUFB3) in WT Tregs. Conclusions: Il1rn-/- Foxp3+ Tregs exhibited greater glycolytic capacity and reserve that WT Tregs. This finding is consistent with the superiority of Il1rn-/- Tregs with respect to suppression of T cell proliferation, a capacity associated with glycolysis

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IL-1β-driven osteoclastogenic Tregs accelerate bone erosion in arthritis.

Project description:IL-1β is a proinflammatory mediator with roles in innate and adaptive immunity. Here we show that IL-1β contributes to autoimmune arthritis by inducing osteoclastogenic capacity in Tregs. Using mice with joint inflammation arising through deficiency of the IL-1 receptor antagonist (Il1rn-/-), we observed that IL-1β blockade attenuated disease more effectively in early arthritis than in established arthritis, especially with respect to bone erosion. Protection was accompanied by a reduction in synovial CD4+Foxp3+ Tregs that displayed preserved suppressive capacity and aerobic metabolism but aberrant expression of RANKL and a striking capacity to drive RANKL-dependent osteoclast differentiation. Both Il1rn-/- Tregs and wild-type Tregs differentiated with IL-1β accelerated bone erosion upon adoptive transfer. Human Tregs exhibited analogous differentiation, and corresponding RANKLhiFoxp3+ T cells could be identified in rheumatoid arthritis synovial tissue. Together, these findings identify IL-1β-induced osteoclastogenic Tregs as a contributor to bone erosion in arthritis.

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Transcription profiling of mouse osteoclastogenic splenocytes

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ATAC-seq data from naïve Tregs, memory Tregs and CD161+ Tregs

Project description:ATAC-seq data from naïve Tregs, memory Tregs and CD161+ Tregs

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Comparison of saliva from healthy and patients with dental erosion

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