Noncoding RNAs and chronic inflammation: Micro-managing the fire within

Abstract

Inflammatory responses are essential for the clearance of pathogens and the repair of injured tissues; however, if these responses are not properly controlled chronic inflammation can occur. Chronic inflammation is now recognized as a contributing factor to many age-associated diseases including metabolic disorders, arthritis, neurodegeneration, and cardiovascular disease. Due to the connection between chronic inflammation and these diseases, it is essential to understand underlying mechanisms behind this process. In this review, factors that contribute to chronic inflammation are discussed. Further, we emphasize the emerging roles of microRNAs (miRNAs) and other noncoding RNAs (ncRNA) in regulating chronic inflammatory states, making them important future diagnostic markers and therapeutic targets.

Keywords: aging; autoimmunity; chronic inflammation; miRNAs; noncoding RNA.

Figure 1

Mechanisms, anatomical locations, and disease types involving chronic inflammation. Chronic inflammation can be initiated by autoantigens or in response to damage associated molecular patterns (DAMPs). Furthermore, the microbiota – via the action of their metabolites, etc. – as well as the aging process itself have been shown to be involved in certain types of chronic inflammation.

Figure 2

Mechanisms of miRNA function in the immune system. miRNAs can have various functions within the immune system and can act in different manners. A: For example, miR‐146a acts as an anti‐inflammatory miRNA via feedback inhibition of an inflammatory pathway. B: miR‐155, on the other hand, is a pro‐inflammatory miRNA that acts in a feed‐forward manner bolstering the immune response. C: miR‐181a is also a pro‐inflammatory miRNA that acts by inhibiting phosphatases that block the activation of T cell genes thus activating T cells. D: Finally, the miR‐17∼92 cluster is involved in promoting the differentiation of a subset of inflammatory T cells called T follicular helpers cells (T_FH).

Figure 3

Sequential threshold model of age‐dependent diseases linked to miRNA regulated chronic inflammation. During youth, the immune system has little chronic inflammation; however, as the aging process occurs, levels of inflammatory cells, such as T follicular helper cells (T_FH) and germinal center B cells (GCB), start to rise. Once the levels of these cells reach a certain threshold, they trigger increased inflammation and the production of autoantibodies. As levels of autoantibodies rise this might trigger tissue damage, which can accumulate and result in the clinical manifestation of chronic inflammatory diseases.