Oxidative Stress and Epigenetics: miRNA Involvement in Rare Autoimmune Diseases

Abstract

Autoimmune diseases (ADs) such as Sjögren’s syndrome, Kawasaki disease, and systemic sclerosis are characterized by chronic inflammation, oxidative stress, and autoantibodies, which cause joint tissue damage, vascular injury, fibrosis, and debilitation. Epigenetics participate in immune cell proliferation and differentiation, which regulates the development and function of the immune system, and ultimately interacts with other tissues. Indeed, overlapping of certain clinical features between ADs indicate that numerous immunologic-related mechanisms may directly participate in the onset and progression of these diseases. Despite the increasing number of studies that have attempted to elucidate the relationship between miRNAs and oxidative stress, autoimmune disorders and oxidative stress, and inflammation and miRNAs, an overall picture of the complex regulation of these three actors in the pathogenesis of ADs has yet to be formed. This review aims to shed light from a critical perspective on the key AD-related mechanisms by explaining the intricate regulatory ROS/miRNA/inflammation axis and the phenotypic features of these rare autoimmune diseases. The inflamma-miRs miR-155 and miR-146, and the redox-sensitive miR miR-223 have relevant roles in the inflammatory response and antioxidant system regulation of these diseases. ADs are characterized by clinical heterogeneity, which impedes early diagnosis and effective personalized treatment. Redox-sensitive miRNAs and inflamma-miRs can help improve personalized medicine in these complex and heterogeneous diseases.

Association of endometriosis with Sjögren's syndrome: Genetic insights (Review)

“…Thus, several studies have investigated the participation and contribution of miRNAs in endometriosis as well as SS etiopathogenesis ( 204 , 205 ). Notably, various miRNAs have been reported to have a similar expression profile in both diseases, including miR16 ( 203 , 206 - 210 ), miR18a-5p ( 203 , 211 , 212 ), miR19b-3p ( 208 , 213 - 215 ), miR26a-5p ( 208 , 209 , 213 ), miR30c-5p ( 59 , 208 , 209 ), miR122-3p ( 214 , 216 ), miR142 ( 217 , 218 ), miR146a-5p ( 217 , 219 , 220 ), miR155-5p ( 218 , 221 ), miR181a ( 222 - 225 ), miR200b ( 220 , 226 ), miR223-3p ( 203 , 213 ) and miR378a-3p ( 213 , 227 ) ( Table II ).…”

“…miR146a is upregulated in the utopic endometrium of patients with endometriosis compared with controls ( 217 ), and is also upregulated in the PBMCs of patients with SS ( 218 , 220 ). It represents an excellent example of a master regulator as it contributes to numerous aspects of immunity, including the control of cytokine overproduction, the suppression of regulatory T (Treg) cells and the control of TLR signaling in recurrent bacterial infection ( 241 - 243 ).…”

“…Moreover, miR146a is activated by NF-kB that plays a crucial role in controlling the TLR/IFN pathway ( 245 ). In this framework, the elevated expression of miR146a found in PBMCs from patients with SS ( 220 ) is of high importance given that it regulates the inflammatory response (negative regulator) by controlling properly the expression of IRAK1 and TRAF6 genes ( 246 ). Furthermore, elevated miR146a levels have been associated with an increased percentage of Th17 cells in patients with SS compared with healthy subjects ( 247 ).…”

“…This miRNA is considered a key modulator regarding both the innate and adaptive immune response, activated by NF-kB, which is known to control the TLR/IFN pathway ( 245 ), while it further regulates the proliferation and function of B and T cells ( 248 ). miR155-5p is also involved in the regulation of immune cells, particularly in SS ( 220 ).…”

Exosomes in Action: Unraveling Their Role in Autoimmune Diseases and Exploring Potential Therapeutic Applications

“…There are over 100 distinct types of AIDs, which can affect almost any part of the body, including the heart, brain, nerves, muscles, skin, eyes, thyroid, and numerous others. Abnormal autoantibodies are often associated with the diagnosis of AIDs, but the majority of autoantibodies have an unknown origin ( 2 3 ). Although the specific causes of AIDs are diverse and largely unknown, genetic susceptibility, autoimmune, and environmental factors have been identified as being associated with the progression of AIDs ( 4 ).…”