Background/Purpose: Primary Sjögren’s Syndrome (pSS) is a systemic autoimmune disease characterized by lymphocytic infiltration of the salivary and lacrimal glands cells form a large part of the lymphocytic infiltrates observed in salivary and lacrimal gland tissues, particularly in the earlier stages of disease, increasing evidence suggests that Treg cells can suppress and control the autoimmune response to protect the body from autoimmune diseases in humans and in animal models . It is also well known that Treg cells play potent roles in the onset and development of SS, but its roles were controversial. This project aimed to claim its role in pSS by investigating ncRNAs related Treg cell.

Methods: Compared to normal controls, we identified the shared and divergent differentially expressed mRNAs (DEmRNAs), miRNAs (DEmiRNAs) and lncRNAs (DElncRNAs) in salivary glands of  pSS and non-pSS sicca cases by RNA-sequencing and bioinformatics analysis. Functional annotation of DEmRNAs were performed. Both cis and trans-target DEmRNAs of DElncRNAs were identified. The target DEmRNAs of DEmiRNAs were identified as well. The DEmiRNA-DEmRNA-DElncRNA interaction network was constructed. QRT-PCR was performed to validate the slected miRNAs, mRNA and lncRNAs in salivary tissues. Dual-Luciferase Report Gene System was used to confirm the target of miRNA. The ratio of Th17 and Treg cells (FOXP3+CD25+ CD4+ T cell) in salivary were identified by flow cytometry.

Results: According to RNA-sequencing, 1523 DEmRNAs, 821 DElncRNAs and 19 DEmiRNAs were detected in salivary gland of pSS group, compared to non-pSS sicca group. 20 DElncRNAs related Treg cell were detected in 20 paired of salivary glands, and lncRNA-Dleu2 was upregulated in pSS salivary gland(p< 0.001) .After the validation by qRT-PCR, the expression of miR15a/miR16-1 cluster was significant up-regulated in salivary glands of pSS patients (p< 0.001), which was negative related with the FOXp3 mRNA, and positive related with lncRNA-DLEU2. According the bioinformatics analysis and references confirmation, miR15a/miR16-1 located in gene of lncRNA- DLEU2, known as a gene cluster. And dual-Luciferase Report Gene System confirmed Foxp3 is the target of miR15a/miR16-1.Flow cytometry confirmed FOXP3+Treg cells were decreased in salivary gland of pSS, which was positive related with the expression of miR15a and miR16-1.

Conclusion: LncRNA- DLEU2-miR15a/miR16-1 might be responsible for the reduced FOXp3+Treg cell in salivary gland of pSS via targeting FOXp3.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-dleu2-mir-15a-16-1-cluster-inhibit-foxp3-treg-cells-in-salivary-glands-of-pss-via-targeting-foxp3/