Correcting the expression of miRNA-155 represses PP2Ac and enhances the release of IL-2 in PBMCs of juvenile SLE patients.

[familial mediterranean fever]

MicroRNA-155 is involved in immune cell , differentiation , maturation and function . MiR-155 showed variable dysregulated expression in autoimmune diseases such as systemic lupus erythematosus (SLE ) and rheumatoid arthritis (RA ) patients . MiR-155 was previously confirmed to directly target CAMP response element binding protein (CREB ), which was previously identified as a positive regulator of protein phosphatase 2 A (PP 2 A ). PP 2 A is a key negative regulator of interleukin-2 , which is an important immune modulator and was previously shown to be decreased in SLE . In this study we aimed at investigating the regulation of PP 2 A by miR-155 and hence its role in juvenile SLE disease pathogenesis . MiR-155 showed significant downregulation in PBMCs from juvenile SLE and juvenile familial Mediterranean fever (FMF ) and significant upregulation in PBMCs from juvenile idiopathic arthritis (JIA ) patients . In SLE , miR-155 expression was negatively correlated with Systemic Lupus Erythematosus Disease Activity Index (SLEDAI ) score and proteinuria and was positively correlated with white blood cell (WBC ) count . The mRNA of the catalytic subunit of PP 2 A (PP 2 A c ) showed significant upregulation in PBMCs from SLE and FMF but not in JIA patients . Additionally , the relative expression of PP 2 Ac mRNA was positively correlated with SLEDAI score . Forced expression of miR-155 led to decreased relative expression of PP 2 Ac mRNA and increased IL -2 release in cultured-stimulated PBMCs . This study suggests for the first time the possible role of an miR-155 -PP 2 Ac loop in regulating IL -2 release and identifies miR-155 as a potential therapeutic target in juvenile SLE disease through relieving IL -2 from the inhibitory role of PP 2 A .

Diseases
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Diseases presenting "first time" symptom

achondroplasia

acute rheumatic fever

adrenal incidentaloma

adrenomyeloneuropathy

alpha-thalassemia

aniridia

aromatase deficiency

canavan disease

carcinoma of the gallbladder

cholangiocarcinoma

classical phenylketonuria

congenital adrenal hyperplasia

congenital toxoplasmosis

cowden syndrome

cushing syndrome

cutaneous mastocytosis

dedifferentiated liposarcoma

dentin dysplasia

dentinogenesis imperfecta

dracunculiasis

dystrophic epidermolysis bullosa

epidermolysis bullosa simplex

erdheim-chester disease

erythropoietic protoporphyria

esophageal adenocarcinoma

esophageal carcinoma

esophageal squamous cell carcinoma

fabry disease

familial mediterranean fever

gm1 gangliosidosis

harlequin ichthyosis

heparin-induced thrombocytopenia

hirschsprung disease

hodgkin lymphoma, classical

holt-oram syndrome

hydrocephalus with stenosis of the aqueduct of sylvius

junctional epidermolysis bullosa

kabuki syndrome

kallmann syndrome

liposarcoma

locked-in syndrome

lymphangioleiomyomatosis

malignant atrophic papulosis

megacystis-microcolon-intestinal hypoperistalsis syndrome

monosomy 21

neuralgic amyotrophy

oculocutaneous albinism

oligodontia

omenn syndrome

oral submucous fibrosis

papillon-lefèvre syndrome

pendred syndrome

phenylketonuria

primary effusion lymphoma

primary hyperoxaluria type 1

severe combined immunodeficiency

sneddon syndrome

triple a syndrome

trochlear dysplasia

von hippel-lindau disease

waldenström macroglobulinemia

well-differentiated liposarcoma

werner syndrome

wiskott-aldrich syndrome

wolf-hirschhorn syndrome

x-linked adrenoleukodystrophy

zellweger syndrome

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