The amazing healing abilities of a common immune cell type boosted by Treg

Osaka, Japan – Investigators are constantly aiming to identify new therapeutic approaches for regenerative medicine. Recent strategies have focused on harnessing the power of the body’s own tissue healing and repair mechanisms, including anti-inflammatory signaling molecules and immune cells.

Collaborating with Professor Shizuo Akira from IFReC, a research team led by Associate Professor Mikaël Martino from Monash University, who also held a cross-appointment position at Osaka University, recently published a significant advancement in regenerative medicine in Nature Communications.

In a recent article, a team of researchers describe a potential new method involving administering regulatory T cells (Tregs) to enhance tissue healing.

Following tissue injury, certain immune cells initiate a pro-inflammatory response. To prevent chronic inflammation and further damage or disease, there must be a transition to an anti-inflammatory response to complete the healing process. Although scientists have previously attempted to support regenerative medicine by modulating a patient’s own immune cells, recent developments have seen researchers testing the effects of delivering specific cell types that can regulate both the immune system and tissue healing.

“We began exploring administering Tregs for regenerative medicine purposes because they can directly impact other immune cell types called monocytes and macrophages,” says Mikaël Martino, lead author of the study. “Additionally, Tregs can secrete signaling molecules that support tissue healing. Despite their strong potential, few studies have explored using Tregs for such applications.”

In this study, the team used a mouse model to simultaneously examine bone regeneration, muscle regeneration, and skin repair, ensuring the injuries were severe enough that therapeutic intervention was necessary. Using a cell delivery method called fibrin hydrogel, they then locally delivered Tregs to the injured areas.  

“Compared with those administered fibrin hydrogel without Tregs, mice given Tregs showed enhanced bone volume and coverage over injured cranial areas, higher amounts of muscle tissue and larger muscle fiber size, and faster skin wound closure,” explains Shizuo Akira, a senior author of the study.

Further mechanistic investigation indicated that the administered Tregs take on an injury-specific phenotype once in the damaged area. In doing so, the Tregs display increased expression levels of genes related to immunomodulation and tissue healing. Additional experiments demonstrated that the Tregs can cause the monocytes and macrophages in these tissues to switch to an anti-inflammatory state, specifically by secreting signaling molecules such as interleukin-10 (IL-10).

“Interestingly, we observed that when the gene encoding IL-10 is knocked out of the Tregs, their pro-healing effects are lost,” says Martino. “This finding indicates the key role of IL-10 in how these Tregs support tissue repair and regeneration.”

Overall, this study provides evidence of the strong potential of using Tregs as a cell-based therapy for regenerative medicine. These data will help develop innovative treatment methods that can promote tissue healing.

Monash University is one of Osaka University's Global Knowledge Partners, a strategic partnership aimed at developing high-quality and sustainable research and education programs that can contribute to the resolution of global issues. Lead author Mikaël Martino, a key advocate for collaboration between the two universities, emphasized the importance of the strong inter-institutional relationship and cross-appointment system in enabling international researchers like himself to collaborate effectively with scientists at Osaka University.

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The article, “Local administration of regulatory T cells promotes tissue healing,” was published in Nature Communications at DOI: https://doi.org/10.1038/s41467-024-51353-2

About Osaka University
Osaka University was founded in 1931 as one of the seven imperial universities of Japan and is now one of Japan's leading comprehensive universities with a broad disciplinary spectrum. This strength is coupled with a singular drive for innovation that extends throughout the scientific process, from fundamental research to the creation of applied technology with positive economic impacts. Its commitment to innovation has been recognized in Japan and around the world. Now, Osaka University is leveraging its role as a Designated National University Corporation selected by the Ministry of Education, Culture, Sports, Science and Technology to contribute to innovation for human welfare, sustainable development of society, and social transformation.
Website: https://resou.osaka-u.ac.jp/en

About Immunology Frontier Research Center (IFReC), Osaka University
IFReC was established by the support of the World Premier International Research Center Initiative (WPI) in 2007. IFReC aims to overcome immune-related diseases by clarifying the whole picture of the immune system, and has promoted globally competitive fundamental research with excellent researchers from overseas.
Website: https://www.ifrec.osaka-u.ac.jp/en/