Sunday, 14 July 2013

MIR155 macrophages

Epub: Moore et al. Mir-155 as a multiple sclerosis-relevant regulator of myeloid cell polarization. Ann Neurol. 2013 doi: 10.1002/ana.23967.

Objective: To define the functional significance of increased mir-155 expression in myeloid cells in multiple sclerosis. 

Methods: Mir-155 expression levels were measured in CD14+ monocytes from untreated RRMS patients and compared to healthy controls. Similar miRNA analyses were performed in laser-captured CD68+ cells from perivascular (blood-derived macrophages) and parenchymal (microglia) brain regions in both active MS lesions and non-inflammatory cases. Using human adult blood-derived macrophages and brain-derived microglia, in vitro experiments were performed to demonstrate how mir-155 influences polarization state, phenotype and functional properties of myeloid cells, in addition to their ability to subsequently impact adaptive T cell responses. 

Results: In multiple sclerosis, mir-155 expression was significantly increased in both peripheral circulating CD14+ monocytes and active lesions (CD68+ cells) compared to control donor monocytes and parenchymal microglia respectively. In vitro, mir-155 was significantly increased in both M1-polarized primary human macrophages and microglia. Transfection of a mir-155 mimic increased pro-inflammatory cytokine secretion and co-stimulatory surface marker expression in both cell types; mir-155 inhibitors decreased pro-inflammatory cytokine expression. Co-culture experiments demonstrated that allogeneic T cell responses were significantly enhanced in the presence of mir-155 transfected myeloid cells compared to controls. 

Interpretation: Our results demonstrate that mir-155 regulates pro-inflammatory responses in both blood-derived and CNS-resident myeloid cells, in addition to impacting subsequent adaptive immune responses. Differential miRNA expression may therefore provide insight into mechanisms responsible for distinct phenotypic and functional properties of myeloid cells, thus impacting their ability to influence CNS injury and repair.

MicroRNA can modify the actions of gene activation and MIR-155. This study indicates that it can modify macrophage function. There are lots more things that this can do.

1 comment:

    Readers might like to look at paper regarding functions for microRNAs.


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