Immunomodulatory Protein Derived from Parasites Enhances Regeneration in Mice
Researchers here exploit an interesting source of immunomodulatory proteins, parasitic worms that live in the mammalian intestine. The protein of interest inhibits TGF-β signaling, which in turn adjusts the innate immune cells known as macrophages into a more pro-regenerative state at a site of injury. This enables regeneration of injuries with a lesser degree of scarring. In skin, hair follicles regrow rather than being replaced by scar tissue, for example. Most of the approaches demonstrated to enhance regeneration in animal models should in principle have some application to the problem of reduced capacity for healing in older people, so it is worth keeping an eye on this part of the field of regenerative medicine.
The balance between scarring and successful tissue regeneration is strongly influenced by immune cells recruited to the wound site, and many researchers are interested in finding ways to boost the activity of immune cell types that promote regeneration while inhibiting the activity of immune cells that promote tissue scarring. Recent studies have suggested that molecules secreted by parasitic worms might modulate the host's immune system in ways that promote tissue regeneration.
In a new study, researchers investigated a protein called TGF-β mimic (TGM) that is produced by Heligmosomoides polygyrus, a parasitic roundworm that lives in the intestines of mice and other rodents. The researchers found that daily topical applications of TGM accelerated the closure of skin wounds in mice. Moreover, TGM treatment reduced the formation of scar tissue while enhancing skin regeneration. For example, unlike untreated animals, TGM-treated mice were able to form new hair follicles within the wounded region of the skin.
The researchers determined that TGM works by binding to a signaling protein, called the TGF-β receptor, that is found on the surface of many cell types in mice and humans, including immune cells. TGM treatment appears to stimulate the recruitment of immune cells known as macrophages into wounds and reprograms them to promote tissue regeneration.