A Long Noncoding RNA Involved in Activation and Repression of Immune Genes

The human body’s immune-based response to the presence of deleterious microbes engages a very intricate and complex system that has evolved over many millions of years.  In this regard, we share many aspects in common with the entire vertebrate world.   Immunity can be regarded as consisting of two categories of responses – innate and adaptive.  In the present discussion, we will focus our attention on the innate immune system.

   

The innate immune system has the extraordinary capability of recognizing a wide range of microbes and inducing the production of many proteins that become engaged in an elaborate defense against the invading organism and ultimately involve the adaptive response.  Over many years of concerted research efforts, it has been shown that the molecular basis of this recognition system involves a host of genetically determined pattern recognition receptors – an example being the so-called “Toll-like receptors” (TLRs).  It is the binding to these receptors that triggers a cascade of immune responses.

It has recently been discovered that long non-coding RNAs (lncRNAs) play a significant role in this process.  As a class of biologically active compounds, literally thousands of these lncRNAs have been discovered in mammalian genomes and they have been shown to regulate gene expression in a number of biological processes.   It is, therefore, of some interest to determine whether lncRNAs play a role in the innate immune system as well.

The work of Dr. Susan Carpenter and her colleagues at the Division of Infectious Diseases and Immunology in the Department of Medicine at the University of Massachusetts Medical School has helped answer this question.  The efficacy of the antimicrobial innate defense is wholly dependent upon the induction of inflammatory gene expression.   Implicated in this complex response is the activation of transcription factors, transcription co-regulators and other factors.

Carpenter and her associates have found that the activation of TLRs – as described previously – induce the expression of many lncRNAs and one of these – lincRNA-Cox2 – has been shown to be involved in the activation and repression of distinct groups of immune-related genes.  This finding is significant in that it helps to further elucidate the mechanism that underlies the innate immune response.