Researchers led by Yasuhiro Murakawa at the RIKEN Center for Integrative Medical Sciences (IMS) and Kyoto University in Japan and IFOM ETS in Italy have discovered several rare types of helper T cells that are associated with immune disorders such as multiple sclerosis, rheumatoid arthritis, and even asthma. Published July 4 in Science, the discoveries were made possible by a newly developed technology they call ReapTEC, which identified genetic enhancers in rare T cell subtypes that are linked to specific immune disorders. The new T cell atlas is publicly available and should help in the development of new drug therapies for immune-mediated diseases.

Helper T cells are kind of white blood cell that make up a large part of the immune system. They recognize pathogens and regulate the immune response. Many immune-mediated disease are caused by abnormal T cell function. In autoimmune diseases like multiple sclerosis, they mistakenly attack parts of the body as if they were pathogens. In the case of allergies, T cells overreact to harmless substances in the environment like pollen. We know of several common T cells, but recent studies have shown that rare and specialized types of T cells exist, and they might be related to immune-mediated diseases.

Within all cells, including T cells, there are regions of DNA called “enhancers”. This DNA does not code for proteins. Instead, it codes for small pieces of RNA, and enhances the expression of other genes. Variations in T cell enhancer DNA therefore lead to differences in gene expression, and this can affect how T cells function. Some enhancers are bidirectional, which means that both strands of the DNA are used as templates for enhancer RNA. The researchers from several different laboratories at RIKEN IMS, as well as colleagues at other institutes, teamed up to develop the new ReapTEC technology and look for connections between bidirectional T cell enhancers and immune diseases.

After analyzing about a million human T cells, they found several groups of rare T cell types, accounting for less than 5% of the total. Applying ReapTEC to these cells identified almost 63,000 active bidirectional enhancers. To figure out if any of these enhancers are related to immune diseases, they turned to genome-wide association studies (GWAS), which have reported numerous genetic variants, called single-nucleotide polymorphisms, that are related to various immune diseases.

When the researchers combined the GWAS data with the results of their ReapTEC analysis, they found that genetic variants for immune-mediated diseases were often located within the bidirectional enhancer DNA of the rare T cells that they had identified. In contrast, genetic variants for neurological diseases did not show a similar pattern, meaning that the bidirectional enhancers in these rare T cells are related specifically to immune-mediated diseases.

Going even deeper into the data, the researchers were able to show that individual enhancers in certain rare T cells are related to specific immune diseases. Overall, among the 63,000 bidirectional enhancers, they were able to identify 606 that included single-nucleotide polymorphisms related to 18 immune-mediated diseases. Lastly, the researchers were able to identify some of the genes that are the targets of these disease-related enhancers. For example, when they activated an enhancer that contained a genetic variant related to inflammatory bowel disease, the resulting enhancer RNA triggered upregulation of the IL7R gene.

“In the short-term, we have developed a new genomics method that can be used by researchers around the world,” says Murakawa. “Using this method, we discovered new types of helper T cells as well as genes related to immune disorders. We hope that this knowledge will lead to a better understanding of the genetic mechanisms underlying human immune-mediated diseases.”

In the long-term, the researchers believe follow-up experiments will be able to identify new molecules that can be used to treat immune-mediated diseases.

Around 34 million years ago, our planet underwent one of the most fundamental climate shifts that still influences global climate conditions today: the transition from a greenhouse world, with no or very little accumulation of continental ice, to an icehouse world, with large permanently glaciated areas. During this time, the Antarctic ice sheet built up. How, when and, above all, where, was not yet known due to a lack of reliable data and samples from key regions, especially from West Antarctica, that document the changes in the past. Researchers from the Alfred Wegener Institute, Helmholtz Centre for Polar and Marine Research (AWI) have now been able to close this knowledge gap, together with colleagues from the British Antarctic Survey, Heidelberg University, Northumbria University (UK), and the MARUM — Center for Marine Environmental Sciences at the University of Bremen, in addition to collaborators from the Universities in Aachen, Leipzig, Hamburg, Bremen, and Kiel, as well as the University of Tasmania (Australia), Imperial College London (UK), Université de Fribourg (Switzerland), Universidad de Granada (Spain), Leicester University (UK), Texas A&M University (USA), Senckenberg am Meer, and the Federal Institute for Geosciences and Natural Resources in Hanover, Germany.

Based on a drill core that the researchers retrieved using the MARUM-MeBo70 seafloor drill rig in a location offshore the Pine Island and Thwaites glaciers on the Amundsen Sea coast of West Antarctica, they were able to establish the history of the dawn of the icy Antarctic continent for the first time. Surprisingly, no signs of the presence of ice can be found in this region during the first major phase of Antarctic glaciation. “This means that a large-scale, permanent first glaciation must have begun somewhere in East Antarctica,” says Dr Johann Klages, geologist at the AWI who led the research team. This is because West Antarctica remained ice-free during this first glacial maximum. At this time, it was still largely covered by dense broadleaf forests and a cool-temperate climate that prevented ice from forming in West Antarctica.

East and West Antarctica react very different to external conditions

In order to better understand where the first permanent ice formed in Antarctica, the AWI paleoclimate modelers combined the newly available data together with existing data on air and water temperatures and the occurrence of ice. “The simulation has supported the results of the geologists’ unique core,” says Prof Dr Gerrit Lohmann, paleoclimate modeler at the AWI. “This completely changes what we know about the first Antarctic glaciation.” According to the study, the basic climatic conditions for the formation of permanent ice only prevailed in the coastal regions of the East Antarctic Northern Victoria Land. Here, moist air masses reached the strongly rising Transantarctic Mountains — ideal conditions for permanent snow and subsequent formation of ice caps. From there, the ice sheet spread rapidly into the East Antarctic hinterland. However, it took some time before it reached West Antarctica: “It wasn’t until about seven million years later that conditions allowed for advance of an ice sheet to the West Antarctic coast,” explains Hanna Knahl, a paleoclimate modeler at the AWI. “Our results clearly show how cold it had to get before the ice could advance to cover West Antarctica that, at that time, was already below sea level in many parts.” What the investigations also impressively show is how different the two regions of the Antarctic ice sheet react to external influences and fundamental climatic changes. “Even a slight warming is enough to cause the ice in West Antarctica to melt again — and that’s exactly where we are right now,” adds Johann Klages.

The findings of the international research team are critical for understanding the extreme climate transition from the greenhouse climate to our current icehouse climate. Importantly, the study also provides new insight that allows climate models to simulate more accurately how permanently glaciated areas affect global climate dynamics, that is the interactions between ice, ocean and atmosphere. This is of crucial importance, as Johann Klages says: “Especially in light of the fact that we could be facing such a fundamental climate change again in the near future.”

Using new technology to gain unique insights

The researchers were able to close this knowledge gap with the help of a unique drill core that they retrieved during the expedition PS104 on the research vessel Polarstern in West Antarctica in 2017. The MARUM-MeBo70 drill rig developed at MARUM in Bremen was used for the first time in Antarctica. The seabed off the West Antarctic Pine Island and Thwaites glaciers is so hard that it was previously impossible to reach deep sediments using conventional drilling methods. The MARUM-MeBo70 has a rotating cutterhead, which made it possible to drill about 10 meters into the seabed and retrieve the samples.

The research project, and the Polarstern expedition PS104 in particular, was funded by the AWI, MARUM, the British Antarctic Survey, and the NERC UK-IODP Programme.

Lunar swirls have defied easy explanation, but recent modeling and spacecraft data shed light on the twisty mystery. The data shows that rocks in the swirls are magnetized, and these rocks deflect or redirect solar wind particles that constantly bombard the Moon. Nearby rocks take the hit instead. Over time, neighboring rocks become darkened by chemical reactions caused by the collisions, while the swirls remain light colored.

But how did the rocks in lunar swirls get magnetized? The Moon does not have a magnetic field today. No astronaut or rover has yet visited a lunar swirl to investigate.

“Impacts could cause these types of magnetic anomalies,” said Michael J. Krawczynski, an associate professor of earth, environmental and planetary sciences in Arts & Sciences at Washington University in St. Louis. He notes that meteorites regularly deliver iron-rich material to areas on the Moon’s surface. “But there are some swirls where we’re just not sure how an impact could create that shape and that size of thing.”

Krawczynski believes it’s more likely that something else has locally magnetized the swirls.

“Another theory is that you have lavas underground, cooling slowly in a magnetic field and creating the magnetic anomaly,” said Krawczynski, who designed experiments to test this explanation. His results are published in the Journal of Geophysical Research: Planets.

Krawczynski and study first author Yuanyuan Liang, who recently earned her PhD in earth, environmental and planetary sciences in Arts & Sciences, measured the effects of different combinations of atmospheric chemistry and magmatic cooling rates on a mineral called ilmenite to see if they could produce a magnetizing effect.

“Earth rocks are very easily magnetized because they often have tiny bits of magnetite in them, which is a magnetic mineral,” Krawczynski said. “A lot of the terrestrial studies that have focused on things with magnetite are not applicable to the Moon, where you don’t have this hyper-magnetic mineral.”

But ilmenite, which is abundant on the Moon, can also react and form particles of iron metal, which can be magnetized under the right conditions, Krawczynski and his team found.

“The smaller grains that we were working with seemed to create stronger magnetic fields because the surface area to volume ratio is larger for the smaller grains compared to the larger grains,” Liang said. “With more exposed surface area, it is easier for the smaller grains to undergo the reduction reaction.”

“Our analog experiments showed that at lunar conditions, we could create the magnetizable material that we needed. So, it’s plausible that these swirls are caused by subsurface magma,” said Krawczynski, who is a faculty fellow in the university’s McDonnell Center for the Space Sciences.

Determining the origin of lunar swirls is considered key in understanding what processes have shaped the lunar surface, the history of a magnetic field on the Moon and even how the surfaces of planets and moons generally affect the space environment surrounding them.

This study will help interpret data acquired by future missions to the Moon, especially those that explore magnetic anomalies on the lunar surface. NASA intends to send a rover to the lunar swirl area known as Reiner Gamma in 2025 as part of the Lunar Vertex mission.

“If you’re going to make magnetic anomalies by the methods that we describe, then the underground magma needs to have high titanium,” Krawczynski said. “We have seen hints of this reaction creating iron metal in lunar meteorites and in lunar samples from Apollo. But all of those samples are surface lava flows, and our study shows cooling underground should significantly enhance these metal-forming reactions.”

For now, his experimental approach is the best way to test predictions about how unseen lava may be driving the magnetic effects of the mysterious lunar swirls.

“If we could just drill down, we could see if this reaction was happening,” Krawczynski said. “That would be great, but it’s not possible yet. Right now, we’re stuck with the surface.”