Naslov
Integrative mRNA/microRNA analysis reveals deregulated RORC/miR-106a-5p circuit in T cells of patients with Hashimoto's thyroiditis

Autori
Štefanić, Mario ; Tokić, Stana ; Glavaš-Obrovac, Ljubica

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
HLA (Immune Response Genetics) / Steven, G. E. Marsh - Lisabon, 2019, 265-266

Skup
33rd European Immunogenetics and Histocompatibility Conference

Mjesto i datum
Lisabon, Portugal, 08.05.2019. - 11.05.2019

Vrsta sudjelovanja
Pozvano predavanje

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
T-lymphocytes, gene expression, microRNA, Hashimoto disease

Sažetak
Hashimoto’s thyroiditis (HT) is the most prevalent autoimmune thyroid disease, characterized by gradual destruction of thyroid follicular architecture. The relationship between inflammation and thyroid damage is complex, and further research is necessary to elucidate by which mechanisms immune cells contribute to the inflammatory response. We here focus on type 17 innate-like T cells by probing a part of their core transcriptional program in blood T cells of 11 controls and 35 patients representing the full spectrum of disease severities. We assessed mRNA expression levels of several transcription factors (RUNX3, RORC, FOXO1, PLZF) and their regulating microRNAs (hsa-miR-106a-5p, 20a, 301a, let-7a) by using immunomagnetic selection, and quantitative real-time PCR [data normalized to TBP or hsa-miR-192-5a endogenous controls, 2(- delta delta Ct) method]. Increasing disease severity was notable for simultaneous enrichment of cytotoxic (RUNX3, median 1.51- fold change, P=0.014), type 17 (RORC, 1.72- fold, P=0.0071) and innate immune genes (ZBTB16/PLZF, 1.92-fold, P=0.014, Kruskal- Wallis test). A reciprocal relationship between the degree of RORC induction in total T cells, and the level of differential underrepresentation of hsa-miR-106a-5p (-1.5 fold, P=0.0011) in severe, hypothyroid HT, was also noted (Spearman's rho=-0.46, P=0.0081). The most significant aging-related transcriptomic change was an upregulation of genes related to cytotoxic/CD8 functions (RUNX3, Spearman's rho=0.45, P=0.0067). In conclusion, blood T cells from aged HT patients show a profound RUNX3+ signature. In addition, circulating T cells from severe HT were apparently skewed towards innate- like lineages, closely mirroring co-alterations in RORC/miR-106a circuitry. The detailed mechanism behind this process and the culprit cell populations underlying convergent transcriptional trajectories remain to be established.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Temeljne medicinske znanosti, Kliničke medicinske znanosti

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