ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1848

Characterization of Treg Phenotype, Function and Its Transcriptome Signatures in Treatment-naïve Rheumatoid Arthritis

Vallayyachari Kommoju1, Sree Nethra Bulusu2, Shruthi S Vembar3, Chengappa Kavadichanda4, Molly Thabah5, Christina Mary Mariaselvam2 and Vir Singh Negi6, 1JIPMER, Pondicherry, India, 2JIPMER, Pondicherry, Puducherry, India, 3IGIB, Bengalore, India, 4Jawaharlal Institute of Postgraduate Medical Education and Research, pondicherry, Puducherry, India, 5Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, Puducherry, India, 6AIIMS, Bilaspur, Puducherry, Puducherry, India

Meeting: ACR Convergence 2024

Keywords: , , , ,

Session Information

Date: Monday, November 18, 2024

Title: T Cell Biology & Targets in Autoimmune & Inflammatory Disease Poster

Session Type: Poster Session C

Session Time: 10:30AM-12:30PM

Background/Purpose: Inflammatory cytokines in the periphery can affect Treg stability and function by altering its molecular signatures. We aimed to characterize Treg phenotype, function and its transcriptome signatures in female, treatment-naïve Rheumatoid Arthritis (RA)

Methods: Treg, Th1-like, and Th17-like Treg frequencies and cytokine levels were quantified in peripheral blood (PB) of RA, Osteoarthritis (OA), and healthy controls (HC) (n=20 each) using fluorescent cytometry. RNA sequencing (n=3 per group) of Tregs was done using Illumina NovaSeq 6000. Differential gene expression was analyzed using DESeq2. Gene networks and hub genes were identified using Cytohubba

Results: Percentage of Tregs in RA was significantly lower than OA and HC. Tregs expressing CXCR3 (Th1-like Tregs) (p=0.001) and CCR6 (Th17-like Tregs) (p=0.001) were higher in RA compared to OA and HC(Table1). RA Tregs displayed reduced suppressive function compared to OA and HC (55.2% vs 79.2% vs 86.3%; (Figure1A&B). Cytokines IL-12, IL-6, IFN-γ and IL-17A were higher in RA compared to HC (Figure1C). Compared to HC, 12268 and 2728 genes were differentially expressed in RA and OA Tregs respectively (Figure1D). Specifically, expression of cytokine receptors, JAK-STAT signalling pathway and PI3/AKT signalling pathway genes were upregulated in RA (Table2, Figure1E).  STAT3, AKT1, NFKB1 and STAT1 were identified as the top 10 hub-genes in RA Tregs (Figure1F).

Conclusion: Phenotypic analysis showed dysregulated Tregs and inflammatory cytokine levels  and transcriptomic analysis revealed upregulation of cytokine-mediated JAK-STAT and PI3/AKT signalling pathways, likely promoting Treg trans-differentiation to Th-like Tregs. The potential to therapeutically target the identified hub genes warrants further research.

Supporting image 1

Table 1: Treg and Th like Tregs percentages in RA, OA and HC peripheral blood. Values are expressed as mean ± standard deviation. The difference between the groups was assessed by student t-test; p<0.05 was considered as statistically significant.

Supporting image 2

Figure 1: (A) CFSE proliferation assay; histogram representing the percentage of proliferating, Teff cells alone and in the presence of RA pTregs, OA pTregs, HC pTregs; (B) Percentage suppression of Teff cell proliferation by RA & OA pTregs Vs HC pTregs (C) Comparison of cytokine levels in RA and HC peripheral blood. Differential expression analysis: (D) volcano plot of RA vs HC (left) and OA vs HC (right); (E) List of pathways enriched in RA Tregs compared to HC (F) Hub genes and the top ten protein interactions

Supporting image 3

Table 2: List of DEGs pertaining to Tregs transdifferentiation in RA and OA. Treg: regulatory T cells, Th1-like Tregs: Tregs expressing Th1 surface marker (CXCR3), Th17-like Tregs: Tregs expressing Th17 surface marker (CCR6), RA: Rheumatoid arthritis; OA: Osteoarthritis; PB: Peripheral blood.

Disclosures: V. Kommoju: None; S. Bulusu: None; S. Vembar: None; C. Kavadichanda: None; M. Thabah: None; C. Mariaselvam: None; V. Negi: None.

To cite this abstract in AMA style:

Kommoju V, Bulusu S, Vembar S, Kavadichanda C, Thabah M, Mariaselvam C, Negi V. Characterization of Treg Phenotype, Function and Its Transcriptome Signatures in Treatment-naïve Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2024; 76 (suppl 9). https://acrabstracts.org/abstract/characterization-of-treg-phenotype-function-and-its-transcriptome-signatures-in-treatment-naive-rheumatoid-arthritis/. Accessed .

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