Stem cells contained within the human body can differentiate into many different types of cells, in some cases regenerating or repairing tissue. Hematopoietic stem cells (HSCs), commonly known as blood stem cells, are found in the bone marrow where they produce platelets, red blood cells, and white blood cells which are also known as the cells of the immune system. Even though this production of white blood cells plays an enormous part in host immunity, it was assumed HSCs only had a one-dimensional role in the immune system involving no prior feedback or memory. Now, a study from researchers led by TU Dresden shows blood stem cells keep a record of previous infections on their DNA to produce a rapid response when infections return. The team states their discovery could help to develop novel vaccines, and therapeutics to counteract an underperforming or over-reacting immune system. The study is published in the journal Cell Stem Cell.
Previous studies show the immune system is known to have an inbuilt memory enabling an improved response to returning pathogens. In the past, the widely held consensus was that HSCs were unspecialized cells, unresponsive to external signals produced by infectious invaders, with their specialized progeny the only cells endowed with the capacity to sense and memorize pathogens to activate immunity. However, recent studies from the group showed HSCs can in fact sense foreign signaling to specifically produce immune cells on demand when faced with a pathogenic invasion. The current study investigates the mechanisms of HSC response to repeat infection.
The current study shows HSCs drive a more rapid and efficient immune response if they were previously been exposed to lipopolysaccharide (LPS), an endotoxin found in the outer membrane of Gram-negative bacteria. Results show the first exposure to LPS causes epigenetic marks on the DNA of the stem cells, in the same genomic region responsible for immune response. Data findings indicate the epigenetic marks of methylation at this point of the HSC’s DNA ensure this genomic region is easily identified and accessed, like recorded data, to activate the salient rapid response when the pathogen returns.
Results show C/EBPb, a protein-based transcription factor important for emergency immune responses, is responsible for the LPS-induced epigenetic marks and gene expression. The lab explains this immune memory which enables the immune system to respond more rapidly when the same pathogen invades again is the foundation of vaccination. They go on to add now it is clear how HSCs record immune response sequences, it should be possible to broaden the protection against foreign bodies.
The team surmises they have discovered blood stem cells register epigenetic marks on their DNA memorizing previous infections to boost immunity. For the future the researchers state their work establishes a central role for HSCs in immune memory, providing new targets and strategies for immunotherapies and vaccination.
Source: Technische Universität Dresden
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