Stem cells: what do bones have to do with boosting immunity?

Stem cells: what do bones have to do with boosting immunity?
© iStock/ Shidlovski

A newly discovered memory that is stored in our bones has revealed the surprising role of stem cells in boosting our immunity.

A  research team led by Professor Michael Sieweke, from the Center for Regenerative Therapies TU Dresden (CRTD) and the Center of Immunology of Marseille Luminy (CNRS, INSERM, Aix-Marseille University), has uncovered a surprising property of blood stem cells that contributes to boosting our immunity.

Not only do the stem cells ensure the continuous renewal of blood cells and contribute to the immune response triggered by an infection, but they can also remember previous infectious encounters to drive a more rapid and more efficient immune response in the future.

These cells are found within the soft tissue, or bone marrow, in the centre of large bones such as the hip and thigh bones.

The new findings should have a significant impact on future vaccination strategies and pave the way for new treatments of an underperforming or over-reacting immune system.

Stem cells’ role in boosting immunity

Stem cells in our bodies act as reservoirs of cells that divide to produce new stem cells, as well as a myriad of different types of specialised cells that are required to secure tissue renewal and function.

Commonly called “blood stem cells”, the hematopoietic stem cells (HSC) are found in the bone marrow, the soft tissue that is in the centre of large bones such as the hips or thighs. The role of the cells  is to renew the repertoire of blood cells, including cells of the immune system, which are crucial to fight infections and other diseases.

Work from Professor Michael Sieweke’s laboratory and others over the past years has proven the dogma that HSCs were unspecialised cells, blind to external signals such as infections, was wrong, and has shown that HSCs can actually sense external factors to specifically produce subtypes of immune cells ‘on demand’ to fight an infection.

Responding to infections

Beyond their role in an emergency immune response, the question remained as to the function of HSCs in responding to repeated infectious episodes. The immune system is known to have a memory that allows it to better respond to returning infectious agents. The present study now establishes a central role for blood stem cells in this memory.

Professor Michael Sieweke, Humboldt Professor at TU Dresden, CNRS Research Director and last author of the publication, explained how they found the memory was stored within the cells: “The first exposure to LPS causes marks to be deposited on the DNA of the stem cells, right around genes that are important for an immune response. Much like bookmarks, the marks on the DNA ensure that these genes are easily found, accessible and activated for a rapid response if a second infection by a similar agent was to come.”

The authors further explored how the memory was inscribed on the DNA, and found C/EBPb to be the major actor, describing a new function for this factor, which is also important for emergency immune responses. Together, these findings should lead to improvements in tuning the immune system or better vaccination strategies.

Sieweke concluded: “The ability of the immune system to keep track of previous infections and respond more efficiently the second time they are encountered is the founding principle of vaccines.

“Now that we understand how blood stem cells bookmark immune response circuits, we should be able to optimise immunisation strategies to broaden the protection to infectious agents. It could also more generally lead to new ways to boost the immune response when it underperforms or turn it off when it overreacts.”

The results of this research are published in Cell Stem Cell on March 12, 2020.

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