Dataset Information

Extracellular MicroRNA Signature of Human Helper T Cell Subsets in Health and Autoimmunity.

ABSTRACT: Upon T cell receptor stimulation, CD4⁺ T helper (Th) lymphocytes release extracellular vesicles (EVs) containing microRNAs. However, no data are available on whether human CD4⁺ T cell subsets release EVs containing different pattern of microRNAs. The present work aimed at filling this gap by assessing the microRNA content in EVs released upon in vitro T cell receptor stimulation of Th1, Th17, and T regulatory (Treg) cells. Our results indicate that EVs released by Treg cells are significantly different compared with those released by the other subsets. In particular, miR-146a-5p, miR-150-5p, and miR-21-5p are enriched, whereas miR-106a-5p, miR-155-5p, and miR-19a-3p are depleted in Treg-derived EVs. The in vitro identified EV-associated microRNA signature was increased in serum of autoimmune patients with psoriasis and returned to healthy levels upon effective treatment with etanercept, a biological drug targeting the TNF pathway and suppressing inflammation. Moreover, Gene Set Enrichment Analysis showed an over-representation of genes relevant for T cell activation, such as CD40L, IRAK1, IRAK2, STAT1, and c-Myb in the list of validated targets of Treg-derived EV miRNAs. At functional level, Treg-derived (but not Th1/Th17-derived) EVs inhibited CD4⁺ T cell proliferation and suppressed two relevant targets of miR-146a-5p: STAT1 and IRAK2. In conclusion, our work identified the miRNAs specifically released by different human CD4⁺ T cell subsets and started to unveil the potential use of their quantity in human serum to mark the pathological elicitation of these cells in vivo and their biological effect in cell to cell communication during the adaptive immune response.

SUBMITTER: Torri A

PROVIDER: S-EPMC5314185 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Extracellular MicroRNA Signature of Human Helper T Cell Subsets in Health and Autoimmunity.

Torri Anna A Carpi Donatella D Bulgheroni Elisabetta E Crosti Maria-Cristina MC Moro Monica M Gruarin Paola P Rossi Riccardo L RL Rossetti Grazisa G Di Vizio Dolores D Hoxha Mirjam M Bollati Valentina V Gagliani Cristina C Tacchetti Carlo C Paroni Moira M Geginat Jens J Corti Laura L Venegoni Luigia L Berti Emilio E Pagani Massimiliano M Matarese Giuseppe G Abrignani Sergio S de Candia Paola P

The Journal of biological chemistry 20170111 7

Upon T cell receptor stimulation, CD4+ T helper (Th) lymphocytes release extracellular vesicles (EVs) containing microRNAs. However, no data are available on whether human CD4+ T cell subsets release EVs containing different pattern of microRNAs. The present work aimed at filling this gap by assessing the microRNA content in EVs released upon in vitro T cell receptor stimulation of Th1, Th17, and T regulatory (Treg) cells. Our results indicate that EVs released by Tr ...[more]

PMID: 28077577

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Project description:Sarcoidosis is a systemic granulomatous disease that develops due to the Th1, Th17 and Treg lymphocytes disturbance. There is an assumption, that B cells and follicular T-helper (Tfh) cells may play an important role in this disorder, as well as in several other autoimmune diseases. The aim of this study was to determine CD19+ B cells subset distribution in the peripheral blood and to define disturbance in the circulating Tfh cells subsets in patients with sarcoidosis. The prospective comparative study was performed in 2016-2018, where peripheral blood B cell subsets and circulating Tfh cell subsets were analyzed in 37 patients with primarily diagnosed sarcoidosis and 35 healthy donors using multicolor flow cytometry. In the results of our study we found the altered distribution of peripheral B cell subsets with a predominance of "naïve" (IgD + CD27-) and activated B cell (Bm2 and Bm2') subsets and a decreased frequency of memory cell (IgD+ CD27+ and IgD- CD27+) in peripheral blood of sarcoidosis patients was demonstrated. Moreover, we found that in sarcoidosis patients there are increased levels of B cell subsets, which were previously shown to display regulatory capacities (CD24+++ CD38+++ and CD5 + CD27-). Next, a significantly higher proportion of CXCR5-expressing CD45RA - CCR7+ Th cells in patients with sarcoidosis in comparison to the healthy controls was revealed, that represents the expansion of this memory Th cell subset in the disease. This is the first study to demonstrate the association between the development of sarcoidosis and imbalance of circulating Tfh cells, especially CCR4- and CXCR3-expressing Tfh subsets. Finally, based on our data we can assume that B cells and Tfh2- and Tfh17-like cells - most effective cell type in supporting B-cell activity, particularly in antibody production - may be involved in the occurrence and development of sarcoidosis and in several other autoimmune conditions. Therefore, we can consider these results as a new evidence of the autoimmune mechanisms in the sarcoidosis development.

Dataset Information

Extracellular MicroRNA Signature of Human Helper T Cell Subsets in Health and Autoimmunity.

Publications

Extracellular MicroRNA Signature of Human Helper T Cell Subsets in Health and Autoimmunity.

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