How The Thymus Regenerates Itself

A molecule called BMP4, that plays a key role in the thymus’s extraordinary natural ability to recover from damage, has been identified in a new study.

The researchers at Fred Hutchinson Cancer Research Center, who conducted the study, hope to translate their work into new therapies to improve the function of the immune system in old age and make immunotherapies more effective.

With advances in cancer immunotherapy splashing across headlines, the immune system’s powerful cancer assassins — T cells — have become dinner-table conversation. But hiding in plain sight behind that “T” is the organ from which they get their name and learn their craft: the thymus.

Thymic Regeneration

The thymus is like a boot camp for new recruits to the immune system. From their birthplace in the bone marrow, immature white blood cells go to the thymus to mature into disease-killing machines.

 thymus

Fred Hutchinson Cancer Research Center

A healthy, active thymus gets you a diverse set of different T cells, each equipped to recognize and kill a slightly different foreign target. Thus, the organ is critical for a strong immune system that’s ready to defend you from any threat.

Although the thymus is sensitive to damage from everything from infections to life stress, it is also naturally resilient. Its power to bounce back from injury, however, fades with age, and it can take a serious hit from certain aggressive cancer therapies.

What if we could harness the thymus’s natural regenerative power to speed its recovery from serious injury, help it stay active with age, and make immune-harnessing drugs work better to fight cancers or infections?

BMP4

BMP4, the molecule identified in the team’s new study, is only the second known driver of natural thymic regeneration.

The first one, called IL22, was discovered by the same research team in 2012. The researchers found that BMP4 is produced by certain cells lining the inside of the organ. That molecule signals other cells of the thymus to turn on genes that promote development and repair.

Now, the team is working to figure out whether there’s a master trigger that activates the whole regeneration process—and then translate that knowledge into new therapies that help patients.

“The thymus is really a bit of a forgotten organ. Everyone works on T cells, but not many care about where they come from. But we would argue that it’s pretty important,”

said Dr. Jarrod Dudakov of FHCC.

Dudakov and colleagues at Memorial Sloan Kettering Cancer Center co-led the research, with collaborators at several other institutions. It was funded by the National Institutes of Health, with additional support from a variety of private donors, philanthropic and professional organizations, and government bodies.

Tobias Wertheimer, Enrico Velardi, Jennifer Tsai, Kirsten Cooper, Shiyun Xiao, Christopher C. Kloss, Katja J. Ottmüller, Zeinab Mokhtari, Christian Brede, Paul deRoos, Sinéad Kinsella, Brisa Palikuqi, Michael Ginsberg, Lauren F. Young, Fabiana Kreines, Sophia R. Lieberman, Amina Lazrak, Peipei Guo, Florent Malard, Odette M. Smith, Yusuke Shono, Robert R. Jenq, Alan M. Hanash, Daniel J. Nolan, Jason M. Butler, Andreas Beilhack, Nancy R. Manley, Shahin Rafii, Jarrod A. Dudakov, Marcel R. M. van den Brink
Production of BMP4 by endothelial cells is crucial for endogenous thymic regeneration
Science Immunology 12 Jan 2018: Vol. 3, Issue 19, eaal2736 DOI: 10.1126/sciimmunol.aal2736

Top Image: Normal thymus. Wellcome Collection. CC0