Microscopic particles released by immune cells may play a powerful role in fueling inflammation in the lungs and shine a new light on an unexpected mechanism behind asthma.
University of Alabama at Birmingham researchers detailed their findings in paper, “Small Extracellular Vesicle Signaling and Mitochondrial Transfer Reprogram T Helper Cell Function in Human Asthma,” recently published in Nature Communications.
The groundbreaking study found that small extracellular vesicles (sEVs) — tiny, cell‑derived “packages” that carry biological material — can transfer membrane-bound cell organelles (mitochondria) between immune cells and effectively reprogram how those cells behave and intensify asthma symptoms.
Asthma is a chronic disease driven by inflammation in the airways, but the precise mechanisms behind this process remain complex and only partially understood, according to the study’s authors. Their research focuses on how certain regulatory cells influence CD4+ T helper cells, which are central players in immune responses. In people with asthma, researchers noted that immune cells release sEVs that actively alter T cell function, pushing them toward inflammatory states.
One of the most surprising findings from the study is that these vesicles are not just carrying signaling molecules — but actual mitochondria, the energy-producing structures inside cells.
According to the researchers:
- sEVs released from immune cells in asthma patients can transfer mitochondria into T cells.
- This transfer triggers activation and polarization of T helper cells into inflammatory subtypes, including:
- Th2 cells (linked to allergic inflammation)
- Th17 cells (associated with severe and chronic inflammation)
Researchers described this process as a “rewire” of receiving immune cells, which promotes inflammation versus controlling it.
Additionally, the study found that the transferred mitochondria activate specific signaling pathways inside T cells — most notably the NF‑κB pathway, which is known to drive inflammation.
Authors noted three key insights that include:
- Mitochondrial transfer leads to oxidant-driven signaling.
- This signaling enhances T cell activation and inflammatory response.
- Blocking this pathway significantly reduces T cell activation.
These findings suggest that mitochondrial transfer is not just incidental — it is a central driver of inflammation in asthma, researchers wrote.
To test the biological impact of this mechanism, researchers conducted experiments using a mouse model of asthma. They found that introducing these mitochondria-containing vesicles into the airways:
- Increased allergic airway inflammation
- Enhanced activation of inflammatory T cells
- They assert this provides strong evidence that the process observed in the lab directly contributes to disease severity.
According to researchers, this discovery opens the door to entirely new treatment strategies. For example, they wrote, instead of focusing solely on reducing inflammation after it occurs, future therapies could aim to:
- Block the release or uptake of extracellular vesicles
- Prevent mitochondrial transfer between immune cells
- Target the NF‑κB signaling pathway
Researchers also identified a protein called DRP‑1, which helps package mitochondria into vesicles as a potential therapeutic target. This is important, they said, as many current asthma treatments — including inhalers and biologic drugs — do not work for all patients, especially those with severe disease.
