Expression of a Functional IL-2 Receptor in Vascular Smooth Muscle Cells

Significance

Interleukin-2 (IL-2) is known to play a key role T cell homeostasis, boosting the up-regulation of immune response through multiplication and separation of effector T cell subsets and down-regulation by means of its involvement in survival and development of T regulatory cells.

IL-2 receptor is made up of three subunits: α (CD25), β (CD122),and γ (CD132). β and γ are shared with IL-15 receptor, and the α subunits are distinct. Numerous non-lymphoid cell types express at least two, if not all three of the IL-2 receptor subunits. However, compared to lymphocytes, not much is known about how IL-2 influences the function of non-lymphoid cells such as vascular smooth muscle cells (VSMC), which are involved in many cardiovascular diseases including atherosclerosis, aneurysms, transplant vasculopathy, and restenosis.

To this end, Wright State University scientists Dr. Prakash Arumugam, Dr. Katie Carroll, Dr. Spencer Barnhill, and led by Professor Lucile Wrenshall together with Dr. Scott Berceli at University of Florida, embarked on a study to analyze whether human VSMC express all three subunits of the IL-2R and whether IL-2 influences the function of vascular smooth muscle cells. Their ultimate goal is to understand the regulation and function of IL-2 in blood vessels, and how impairment of either contributes to human vascular pathology. The paucity of research on IL-2R expression on VSMC, plus the lab’s previous research showing that IL-2 is retained in the extraceullular matrix of blood vessels, served as motivation for their study which is now published in Journal of Immunology.

When the research team isolated mRNA from VSMC and amplified it by RT-PCR using intron-spanning primers specific to each component of the IL-2R they found VSMC do indeed express mRNA for IL-2Rα, -β, and –γ.

Furthermore, by using an explant model in which VSMC were allowed to migrate from small pieces of cultured aorta, they found that IL-2 promotes migration and proliferation of VSMC. They also showed IL-2 to activate intracellular signals in these cells. Also, through the incubation of VSMC with IL-2 for 24 hours, there was an increased expression of Fox03a, which suggests that IL-2 impacts the survival of VSMC in vivo.

Interestingly, Arumugam and colleagues suggested that analogous to its role in T cells, the IL-2/ IL-2R system contributes to the balance of VSMC in the vasculature. These findings imply a new connection between the immune and vascular systems, with implications not only for atherosclerosis but for vasculitis and autoimmune diseases as well. Further studies will be of high importance to validate new drug targets and therapeutics to correct VSMC pathology.

Expression of a Functional IL-2 Receptor in Vascular Smooth Muscle Cells - Medicine Innovates

 

About the author

Lucile Wrenshall’s interest in IL-2 stems from her career as both a transplant surgeon and scientist. She received her MD degree from Pennsylvania State University in 1985, and her PhD from the University of Minnesota in 1993. She has approximately 50 articles in peer reviewed journals, and her research has been supported by the Howard Hughes Medical Institute, the Juvenile Diabetes Research Foundation, the American Society of Transplant Surgeons, and the National Institutes of Health. She is a Fellow of the American College of Surgeons and a Fellow of the American Society of Transplantation.

Dr. Wrenshall’s research interests are focused mainly on the interactions of IL-2 with the extracellular matrix and cells comprising blood vessels.

Reference

Arumugam, P., Carroll, K., L., Berceli, S., A., Barnhill, S., Wrenshall, L., E., Expression of a Functional IL-2 Receptor in Vascular Smooth Muscle Cells, J. Immunol. 2019; 202:694-703; doi: 10.4049/jimmunol.1701151

About Priti