Researchers Identify Key Proteins Influencing Major Immune Strategies

New research from the Masonic Cancer Center, the University of Minnesota, and the University of Minnesota Center for Immunology has identified key proteins that influence immune response strategies, a finding that could influence new vaccination approaches. The study, published in the latest edition of Nature Immunology, looked closely at the KLF2 and S1P1 genes, and how their expression impacted the immune strategy of a cell.

The immune system has two main strategies to empower white blood cells, or lymphocytes, to resist infections of the body. The first strategy, called recirculation, is a process where white blood cells are carried around in circulating blood, allowing rapid access to organs once an immune response has begun. The second major strategy allows lymphocytes to migrate into tissues and remain there long-term, creating a kind of rapid response team to any infectious organism that enters the body. These cells are called resident memory T-cells or Trm, and they play a dominant role in initiating immune responses that control infections.

"A key question we had was how lymphocytes make the choice to be a recirculator or a resident," says Stephen Jameson, PhD, a professor in the Center for Immunology and Department of Laboratory Medicine and Pathology in the University of Minnesota Medical School. "We already knew the protein KLF2 regulates the expression of genes. One of those genes, called S1P1, allows lymphocytes to leave tissues and begin recirculating."

Intrigued by the impact of KLF2 and S1P1 on lymphocytes' ability to move out of tissues, Jameson and colleagues wanted to compare resident and recirculating cells and the KLF2 and S1P1 levels. They found that resident T-cells had lost expression of the KLF2 and S1P1 genes.

The next step was finding what controlled the expression of KLF1 and S1P1. Jameson's team was able to pinpoint cytokines as playing a major role in this cell decision-making process.

"Cytokines are soluble proteins that act similar to hormones for the immune system," says Jameson. "We found the cytokines can instruct cells to become resident memory cells, thereby may be useful for bolstering local immunity."

Though further research is needed to define the biochemical signals dictating how recirculation versus residency is chosen, learning more about these key signals instructing T-cells to determine their strategic immunity role could significantly improve vaccination approaches. Researchers may be able to use the knowledge and develop technology to focus memory T-cells to form a barrier to infections.

This project was supported by funding from an NIH MERIT award to Jameson (R37 AI38903) and an NIH training grant for Cara Skon (T32 AI07313), as well as other NIH grants to contributing authors (R37 AI39560 and T90 DE022732).

Source: Center for Immunology,  University of Minnesota