Molecular profiling of regulatory T cells in pulmonary sarcoidosis. (November 2018)

• Record Type: Journal Article
• Authors: Kachamakova-Trojanowska, Neli; Jazwa-Kusior, Agnieszka; Szade, Krzysztof; Kasper, Lukasz; Soja, Jerzy; Andrychiewicz, Anna; Jakiela, Bogdan; Plutecka, Hanna; Sanak, Marek; Jozkowicz, Alicja; Sladek, Krzysztof; Dulak, Jozef
• Is Part Of: Journal of autoimmunity. Volume 94(2018)
• Page Start: 56
• Page End: 69
• Publication Date: 2018-11
• Subjects: miRNA -- RNAseq -- Treg -- Pulmonary sarcoidosis -- Global expression -- TLR; Autoimmunity -- Periodicals; Autoimmune diseases -- Periodicals; Autoantibodies -- Periodicals; Autoimmune Diseases -- Periodicals; Auto-immunité -- Périodiques; Maladies auto-immunes -- Périodiques; Electronic journals; 616.978005
• DOI: 10.1016/j.jaut.2018.07.012
• Languages: English
• ISSNs: 0896-8411

Abstract

Abstract: Background: Sarcoidosis is characterized by exaggerated immune response to unknown agent and can affect different organs. One of the main players in the pathology of the disease are regulatory T cells (Tregs), however, up to date the mechanisms of the possible molecular alterations of this particular cell subset are not known. Methods: In the current study we looked for the global transcriptomic changes of miRNAs, using predefined array, and mRNAs (RNA seq analysis) of Tregs of patients with the most predominant form of the disease - acute pulmonary sarcoidosis (PS). For this purpose sorted CD4+/CD25+/CD127- Tregs from peripheral blood (PB) and CD4+/CD25 + Tregs from bronchoalveolar lavage (BAL) were used. Results: MiRNA analysis revealed that Tregs isolated from PB and BAL display significantly different miRNA profile, suggesting an important role of the pulmonary microenvironment in creating these changes. Among disease-related miRNAs of PB Tregs we identified miR-155 and miR-223. Moreover, looking at the global transcriptome of PB Tregs, we recognized alterations in TLR-2 signaling pathway and in the downstream of NF-κB apoptosis and proliferation signals. However, induction of TLR-2 expression was found not only in Tregs, but also in the heterogeneous population of peripheral blood mononuclear cells (PBMC) as well as two PBMC subpopulations (CD4+/CD25-and CD4-/CD25-) of patients with PS. This indicates that activation of TLR signaling pathway in sarcoidosis does not occur only in Tregs. Conclusion: Our findings offer a deeper insight into the molecular mechanisms of Tregs reduced suppression and increased apoptosis in patients with PS. Based on the current results, future studies should focus on possible therapeutic effect of TLR-2 signaling inhibition. Highlights: Tregs from BAL and peripheral blood (PB) have distinct miRNA expression profiles. Increased expression of miR-155 and -223 marks sarcoidosis PB Tregs. Sarcoidosis PB Tregs have increased FOXP3 and dysregulated TLR-2 signaling. TLR-2/MyD88 expression is upregulated in different PB immune cells in sarcoidosis. RNA seq reveals signs of intrinsic apoptosis induction in sarcoidosis PB Tregs.