The research, which was published in the journal Proceedings of the National Academy of Sciences (PNAS), offers a promising target for future therapies.

Hidradenitis suppurativa (HS) is an immune disease that affects up to 4% of the global population and causes painful, recurring skin lesions and inflammation, primarily in the folds of the skin. It commonly affects women of African American descent.

Shahid Mukhtar and his team — Bharat Mishra, Nilesh Kumar and graduate student YiFei Gou — used single-cell sequencing techniques to pinpoint CD2 as a key immune receptor with elevated expression on T cells and innate lymphoid cells (ILCs), including natural killer cells, in HS-affected skin tissue.

In collaboration with researchers at the University of Alabama at Birmingham, Mukhtar’s team demonstrated through organotypic skin culture experiments from HS patients that blocking CD2 led to a significant reduction in cytokine and chemokine production, along with suppression of key pathogenic gene signatures.

This finding suggests that blocking CD2 may effectively reduce the inflammatory response in HS, providing a potential new therapeutic avenue for managing symptoms and improving patient quality of life.

Gou, who has a keen interest in deep learning, a type of artificial intelligence (AI), hopes to further integrate single-cell transcriptomics with global protein-protein interactions using contextual AI. This approach aims to enhance understanding of cellular networks and disease mechanisms, pushing forward the frontiers of precision medicine for immune-related diseases like HS.

“Our integrative approach, combining single-cell data with molecular insights, shows the transformative potential of multiomics in discovering novel therapeutic targets,” Mukhtar said. “These findings deepen our understanding of HS and open new pathways for developing targeted therapies in HS and other immune-related conditions.”

This discovery has far-reaching implications for our understanding of past climate variability and future climate change. However, lead author and junior professor Dr Sebastian Sippel from Leipzig University stresses that the new findings do not affect the quantification of the global warming relative to 1850-1900 and the human contribution to that warming: the land and ocean temperatures of the 19th century (1850-1900), before the onset of the cold period, provide a physically very consistent picture of temperature changes up to the present day. Nevertheless, correcting this cold period could increase confidence in the amount of observed warming, changing what we know about historical climate variability and improve the quality of future climate models.

Understanding global temperature trends is crucial for climate research. Dr Sebastian Sippel, Junior Professor for Climate Attribution at Leipzig University, worked with international scientists to reconstruct the global mean temperature from historical climate data like a jigsaw puzzle — including historical land and ocean measurements and palaeoclimatic analyses. When comparing land and ocean, Sippel noticed a systematic deviation: at the beginning of the 20th century, ocean temperatures were lower than in previous decades, while over land air temperatures remained relatively constant. This outcome is not consistent with physical theory and climate models.

New explanations for past phenomena

Using many different lines of evidence, the new study shows that reconstructions of the global mean temperature from ocean surface data for this period are too cold: on average about 0.26 degrees Celsius colder than seen in land-based reconstructions. This discrepancy is greater than what would be possible under natural climate variability. “Our latest findings do not change the long-term warming since 1850. However, we can now better understand historical climate change and climate variability,” says junior professor Dr Sebastian Sippel. For example, the reasons for the early 20th century warming period between 1900 and 1950 have never been fully understood. If the ocean temperatures are corrected, the warming trend of the early 20th century is weaker. “The discrepancies between the climate models and the observed temperature trend at the beginning of the 20th century are mainly due to an incomplete understanding of the observations, rather than incomplete climate models or natural climate variability. There are well-established approaches to account for the effects of changing measurement methods on ocean surface temperature measurements. The new research shows that in the early 20th century these methods don’t properly account for very rapidly changing differences in the way the observations were made. Our new understanding confirms the climate models and shows even more clearly the human impact since pre-industrial times,” says co-author Professor Reto Knutti, Professor for Climate Physics at ETH Zurich.

A multidimensional approach

The study itself offers indications that the cause of the ocean cold anomaly could lie in insufficiently documented information about the measurement techniques used at that time. Before the Second World War, ocean temperatures were mainly measured with buckets on ships, but the method of measurement and the composition of ship fleets changed from decade to decade, making it much more difficult to correct for systematic measurement errors. The authors of the study therefore recommend a variety of approaches to data processing and analysis: “Our methodological approach emphasises the need to continuously rescue and digitise historical climate data and compare it with independent data. At the same time, very different assumptions regarding systematic adjustments of early climate data should be tested, as the observational data are of central importance as a basis for climate understanding and modelling,” says Sippel.

The ability of the human heart to renew itself by regenerating its muscle cells, myocytes, is very limited. But what happens to this capability when the heart is damaged by severe heart failure has been unknown.

Researchers at Karolinska Institutet have now discovered that after an injury, the rate of cell renewal is even lower than in a healthy heart. Standard-of-care for patients with advanced heart failure is a surgically implanted pump that helps propel blood, a so-called left ventricular assist device (LVAD).

Kick-start the repair mechanism

Surprisingly, the researchers found that patients with such a heart pump, who have shown significant improvement in their heart function, can regenerate heart muscle cells at a rate more than six times higher than in healthy hearts.

“The results suggest that there might be a hidden key to kick-start the heart’s own repair mechanism,” says Olaf Bergmann, senior researcher at the Department of Cell and Molecular Biology at Karolinska Institutet and last author of the paper.

The mechanism behind the effect is still unknown and there is not yet any hypothesis to explain it.

“It is difficult to say. In the existing data we cannot find an explanation for the effect, but we will now continue to study this process at a cellular and molecular level,” says Olaf Bergmann.

The findings open the possibility of developing new therapies for patients with serious heart conditions that stimulate the heart’s ability to repair itself after damage. This way, patients wouldn’t have torely only on heart transplants or other kinds of long-term mechanical support.

“This offers some hope that the recovery after a heart incident can somehow be boosted,” says Olaf Bergmann.

Determine the age of cells

It is generally difficult to determine the age of cells in the human body and to decide which cells are new and which are old. However, by using a method earlier devised by Jonas Frisén, professor of stem cell research at Karolinska Institutet, the group has been able to count the rate of renewal of myocytes in the heart. The method is based upon the fact that the percentage of radioactive carbon in the atmosphere, and subsequently in our cells, has steadily decreased since the nuclear test ban in 1963. For every following year, there is a little less radioactivity in newly formed cells, which means that they can be ‘dated’.

The study was done in close collaboration with Stavros Drakos at the University of Utah, USA, and was mainly financed by the Swedish Research Council, LeDucq Foundation and the Ragnar Söderberg Foundation. There are no reported conflicts of interest.