Tattoo ink may cause prolonged changes to the immune system

Tattoos have gained widespread popularity, with nearly one in three Americans having at least one. But beneath the colorful designs lurks a hidden journey. According to a new study, tattoo ink doesn’t stay in the skin; it travels and accumulates in the lymph nodes, potentially causing lifelong changes to the immune system. The findings offer no conclusion as to whether these changes are positive or negative, but suggest that pigment retention in lymph nodes can persistently alter local immunity.

“Tattoos are not only a cosmetic treatment, but they are also associated with some important problems like the presence of some inflammation in the immune system, which we need further study [of] in the future,” the first author of the study, Santiago F. Gonzalez, told New Atlas.

A complex admixture of the ink that is insoluble in bodily fluids grants durability to tattoos. While previous studies have linked tattoo ink ingredients to various health issues, research on the interaction of ink components with the immune response is scarce. To evaluate how tattooing affects the immune response, Santiago and his colleagues set up a mouse model.

The researchers tattooed a small 25-square-millimeter patch on the footpads of mice with three commonly used commercial inks (black, red and green). Using advanced microscopy, the team tracked the real-time transport of ink immediately after tattooing. The results revealed that the ink does not stay only in the skin, but gets transported to the lymph nodes. In the lymph nodes, macrophages - immune cells that destroy germs and damaged cells - capture this ink and initiate an inflammatory response.

Within 24 hours, researchers observed a “significant decrease” in the total number of macrophages, indicating that tattoo ink induced macrophage death. The traces of the ink in the lymph node were present even after two months.

The paper hypothesizes that the ink persistence and the macrophage death could affect the capacity of these cells to control the spread of pathogenic viruses and bacteria.

“We are, at the moment, in follow-up studies evaluating these possibilities," Santiago told New Atlas. "We also have to further investigate and see the connection between tattoos and cancer."

Since macrophages are critical to the generation of a robust immune response following vaccination, the team was interested to test vaccines. They injected an mRNA-based COVID-19 vaccine or a UV-inactivated influenza shot directly into the tattooed footpad. For the COVID vaccine, antibody responses against the spike protein weakened. Meanwhile, for the influenza vaccine, the opposite happened: the ink likely amplified the immune response.

Santiago explains that for mRNA-based vaccines, macrophages are needed to capture the vaccine and express the antigens that make the mRNA vaccine work.

“In the tattooed individuals, these macrophages are full of ink; therefore, the ink basically does not allow them (vaccine) to work as they should,” Santiago tells us.

In the case of the influenza vaccine, the response is directed by dendritic cells, not by macrophages.

“These dendritic cells sense the inflammation generated by the dying of the macrophages as some sort of an adjuvant,” Santiago says, explaining why an immune response is possibly amplified by tattoo ink.

Ultimately, Santiago suggested people should generally avoid getting a vaccine shot directly into tattooed skin. And more generally, he suggests people be cautious with the practice of tattooing. There are still a lot of unknowns yet to be researched.

“We don't want to scare the population, obviously, but we want it to have at least some caution with respect to doing more tattoos,” he told us.

The study has been published in Proceedings of the National Academy of Sciences.