Some organs appear to have the immunological equivalent of “neighborhood police”—specialized squads that patrol only one area, a single organ, instead of an entire city, the body.
The research, in mice, finds the liver, skin, and uterus each has dedicated immune cells. Other organs may have similar defenses against cancers and viral infections. The finding could aid efforts to use immune cells to treat illness.
“If, for example, we can use specialized medications to activate only these organ-specific cells, they could provide powerful and selective weapons against infections and tumors in the organs where they reside,” says senior investigator Wayne M. Yokoyama, professor of medicine at Washington University School of Medicine in St. Louis.
“Cells that only defend one organ may be much better equipped than the roaming immune cells to mount an attack and limit collateral damage to healthy tissue.”
Scientists have thought that mature natural killer cells circulate through the body looking for viruses and cancers. When these immune cells identify a threat, they attack.
Scientists also thought that natural killer cells that stayed in the liver instead of circulating were immature or inactive and eventually would become like other natural killer cells, leaving the liver and moving through the body.
In the new study, lead author Dorothy K. Sojka, a postdoctoral research fellow in Yokoyama’s laboratory, shows that some natural killer cells never leave the liver. She also identifies additional tissue-resident natural killer cells in the skin and uterus.
Sojka also experimented with transcription factors—molecular switches that turn a number of genes on and off. Among other results, she found that disabling one of these switches could prevent circulating natural killer cells from developing without affecting tissue-resident natural killer cells in the liver, skin, and uterus. Disabling another transcription factor wiped out the liver and skin tissue-resident natural killer cells while having little effect on the circulating and uterus tissue-resident natural killer cells.
“If one group of cells absolutely needs a specific transcription factor to exist, while another group of cells doesn’t care if that factor is gone, that strongly suggests the two groups of cells use distinct developmental pathways and are therefore different,” Sojka says.
Her results point to at least four types of natural killer cells rather than just the one major type long recognized by immunologists. She is looking for groups of resident natural killer cells in other organs and investigating the origins and functions of those she already has identified.
“Conceptually, this is very different, a significant change in our thinking about how a very important part of the immune system works,” says Yokoyama, a Howard Hughes Medical Institute Investigator.
The National Institutes of Health and National Basic Research Project of China supported the research. The Rheumatic Diseases Core Center performed the speed congenics backcross. The study is published in eLife.