S.M. Henson, R. Aspinall

Thymic involution is one of many events that leads to the inefficient functioning of the elderly immune system, causing an increased susceptibility to numerous infectious diseases. This loss of immune function, can be in part characterized by the loss of the cytokine IL-7. Several investigators have shown that when IL-7 is administered in vivo it can enhance de novo T-cell production by the thymus, but there are several problems with giving IL-7 as a therapy: IL-7 has a short half life making it necessary to give repeated injections and it must be administered at a high enough dose to allow it to reach the thymus. An alternative approach, and one which should reduce dosage levels and treatment frequency, would be to create a fusion protein between IL-7 and a chemokine receptor whose ligand is organ-specific. The chemokine CCL25 is thought to play a major role in T-cell development as an attractant for thymocytes, which express the receptor CCR9. Thymic tissue expresses high levels of CCL25 and CCR9 shows a strict specificity for its ligand CCL25. CCR9 is therefore an ideal choice as a targeting component for IL-7. I show here the creation of a CCR9/IL-7 fusion protein, which retains its IL-7 activity and shows an increased ability to target the thymus.

Keywords (Optional): 
fusion protein
thymic involution