Aberrant expression of microRNAs in T cells from patients with ankylosing spondylitis contributes to the immunopathogenesis

Abstract

Summary Ankylosing spondylitis (AS) is a chronic inflammatory disorder characterized by dysregulated T cells. We hypothesized that the aberrant expression of microRNAs (miRNAs) in AS T cells involved in (TLR-4), a target of let-7i, in T cells from AS patients were decreased. In addition, the mRNA expression of interferon (IFN)-g was elevated in AS T cells. Lipopolysaccharide (LPS), a TLR-4 agonist, inhibited IFN-g secretion by anti-CD3+ anti-CD28 antibodiesstimulated normal T cells but not AS T cells. In the transfection studies, we found the increased expression of let-7i enhanced IFN-g production by anti-CD3 + anti-CD28 + lipopolysaccharide (LPS)-stimulated normal T cells. In contrast, the decreased expression of let-7i suppressed IFN-g production by anti-CD3 + anti-CD28 + LPS-stimulated AS T cells. In conclusion, we found that miR-16, miR-221 and let-7i were over-expressed in AS T cells, but only miR-221 and let-7i were associated with BASRI of lumbar spine. In the functional studies, the increased let-7i expression facilitated the T helper type 1 (IFN-g) immune response in T cells.

miR-573 is a negative regulator in the pathogenesis of rheumatoid arthritis

“…Such a decrease was also observed for other miRNA, e.g., let-7i, miR-125b, and miR-98, in response to LPS treatment. [26][27][28] This phenomenon shows a proinflammatory phenotype as demonstrated by the increase in TLR2 expression, which could exacerbate inflammation by promoting secretion of various cytokines (IL-6 and IL-8) and MMPs release. 29 In particular, TLR2 was confirmed as a direct target of miR-573, and silencing TLR2, but not TXNDC5, could duplicate the miR-573 transfection, as shown strikingly by experiments involving IL-6, TNF-a, and IL-1b, supporting the existence of TLR-2 dependent manner during miR-573 functioned to negatively regulate inflammation in RA.…”

MicroRNA let-7i induced autophagy to protect T cell from apoptosis by targeting IGF1R

“…Previous report has indicated that let-7i is up-regulated in T cells from AS [15]. The let-7 family members have been demonstrated to target directly IGF1R in head and neck cancer cells, prostate cancer cells, hepatocellular carcinoma cells, and spermatogonia [33][34][35].…”

“…For example, inhibition of let-7a decreases production of allergic cytokines and alleviates the phenotype of asthma [14]. Upregulation of let-7i in T cells from AS has been found, which contributes to IFN-c production [15]. All the data suggest the important inflammatory role of miRNA.…”

Increased miR-223 expression in T cells from patients with rheumatoid arthritis leads to decreased insulin-like growth factor-1-mediated interleukin-10 production

“…All the miRNAs were converted to the corresponding cDNAs in a one-step reverse transcription (RT) reaction according to the method developed by Chen et al [17], as described previously [18]. A real-time PCR-based method was used to quantify the expression levels of miRNAs using an ABI Prism 7500 Fast Real-Time PCR system (Applied Biosystems, Foster City, CA, USA).…”