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Tattoos Do Odd Things to the Immune System

ReachMD Healthcare Image
03/25/2023
theatlantic.com

In 2018, I paid a man a couple hundred dollars to repeatedly jam several needles into the skin of my right wrist. I felt as if I were being attacked by a microscopic cavalry of crabs. Into every jab went black ink, eventually forming the shape of double quotation marks. It was my first tattoo, and likely not my last.

In the thousands of years that tattoos have been around, not much has changed. The practice still involves carving wounds into permanent, inked-in shapes that we find aesthetically pleasing. But much of tattooing remains mysterious: Scientists still aren’t sure what makes certain tattoos fade fast, why others stick around when they’re supposed to disappear, or how they react to light. One of the strangest and least-studied enigmas, though, is how tattoos survive at all. Our immune system is constantly doing its darndest to destroy them—and understanding why it fails could clue us in to one of our bodies’ most important functions, even when we leave the skin blank.

When a tattoo is stamped onto skin, the body considers it an assault. The skin is the immune system’s “first barrier,” and is heavily stocked with fast-acting defensive cells that can leap into action when it’s breached, says Juliet Morrison, a virologist at UC Riverside. Those cells’ prime directive is to suss out anything foreign and destroy it so the healing process can begin.

That mission is generally quite successful—allowing burns to heal, scars to fade, and scabs to fall away—except, for some reason, when ink gets involved. The particles in pigments are bulky and difficult for an immune cell’s enzymes to degrade. So when inks get gulped down by immune cells such as skin-dwelling macrophages—which spend their lives devouring pathogens, cellular debris, and other schmutz within just a teeny patch of flesh—it can transform into a microscopic version of gum. The pigment particles lodge themselves inside macrophages’ innards, refusing to be broken down. When ink is visible at the surface of the body, it’s not just interlaced among skin cells—it’s shining out from the bellies of macrophages that can’t digest it.

Read: The benefits of a foreign-language tattoo

Sandrine Henri, an immunologist at France’s Center of Immunology of Marseille-Luminy, and her colleagues have found that macrophages’ taste for ink can help explain why tattoos so tenaciously stick around, even after the cells die. At the end of a macrophage’s days- or weeks-long life, it begins to come apart, releasing the pigment at its core. But that ink then immediately gets snatched up and wolfed down by another macrophage in the vicinity that more or less takes its predecessor’s place, no more than perhaps a few micrometers away—less than the width of a human hair.

Over time, the edges of tattoos may get a bit fuzzier as the ink passes from cell to cell. Some pigment may also end up shuttled to lymph nodes. Those major immunological hubs are normally off-white. But in heavily tattooed people, they can end up turning “the color of the ink,” says Gary Kobinger, an immunologist at the Galveston National Laboratory at the University of Texas Medical Branch. But by and large, the ink stays inside of macrophages, and thus stays put. This infinite relay of ingestion, regurgitation, and reingestion, Henri told me, is thought to be part of the reason it’s so difficult to laser off tattoos—and, potentially, part of the reason some new companies’ “temporary” tattoos haven’t been fading as advertised.

Scientists aren’t yet sure if the macrophages’ inky clog-up has consequences. “What if you are forcing them to take care of these foreign clumps of pigment instead of doing immune surveillance?” Morrison told me. Stopped-up macrophages might be less able to take in more dangerous substances, such as pathogens. One study published last year found that tattoo pigment might alter the proteins they produce and the signals they send to other cells. All of that might mean nothing—or that the cell starts over- or underreacting to foreign material, potentially putting the immune system at a disadvantage if a new tattoo ends up inflamed, infected, or triggering allergies.

Infections are rare with tattoos—at most, they happen 5or 6 percent of the time—and when they do occur, they’re most commonly bacterial. But in very, very rare cases, body-art aficionados can end up with dangerous viruses, including hepatitis C. Thankfully, especially with modern advances in sanitation, most people with tattoos “do just fine,” says Danielle Tartar, a dermatologist at UC Davis.

Henri, for one, isn’t worried: The immune system is multifaceted and constantly replenishing its cells; in the event of a major attack, cells busying themselves with ink would probably be able to call in reinforcements to waylay the threat. And it’s very possible that the macrophages are only temporarily discombobulated by the ink they swallow and end up resetting to a new baseline.

Read: Show your immune system some love

Besides, there’s more to the immune system than the cells that love to chow down on ink. A few years ago, a team of researchers led by Jennifer Juno, an immunologist at the University of Melbourne, in Australia, mixed tattoo ink into a vaccine formulation to track where the contents of the shot ended up in mice and macaques. There was no evidence that the pigments were making immune cells on the whole “unhappy,” Juno told me, or killing them off. Nor did the ink seem to change how well the vaccine worked.

Some small bits of damage to the skin—administered by a professional using sterile, hypoallergenic equipment and materials—could even keep nearby immune cells spry. Studies are now finding that macrophages and other so-called innate immune cells might be able to briefly remember some of their past encounters with other types of foreign material and better respond to future assaults. (This, of course, is the whole point of vaccination, but vaccines target adaptive immune cells, which are much more amenable to the process.) It’s also possible—though not yet borne out by data—that learning to coexist with tattoo ink could help immune cells calibrate their reactions to other substances, perhaps even heading off autoimmune attacks, says Tatiana Segura, a biomaterials expert at Duke University. “If your body tolerates a tattoo at all, it means that the immune system adapted,” says María Daniela Hermida, a dermatologist based in Buenos Aires.

To understand some of the immune effects of tattoos, Christopher Lynn, an anthropologist at the University of Alabama, has been studying heavily inked people in different parts of the world. He and his colleagues have found that individuals who frequently get tattoos appear to have higher levels of certain immune molecules, includingantibodies, in their blood than people who rarely get inked (at least for a brief time). Maybe, Lynn told me, frequent tattooing gives the immune system a regular, low-intensity workout—and keeps certain bits of our defensive armamentarium more fit.

But more antibodies is not the same as better immunity, and the researchers don’t yet have a sense for how long those effects last, says Saranya Wyles, a dermatologist at the Mayo Clinic. And because Lynn and his colleagues haven’t run a clinical trial in which they’ve assigned some people to ink up and others to not, they can’t actually prove that the antibody bump is a direct result of a tattoo. It’s possible, Lynn told me, that people with naturally higher levels of certain immune molecules are more prone to getting tons of tattoos, because they’re less likely to have bad reactions. Tattoos, in that case, would be more of a litmus test for the body—which, in some ways, checks out with the cultural impetus for body art in many cultures: flaunting one’s tolerance for pain. Either way, Lynn cautions that, even in the best-case scenario, tattooing will have its limits. “I don’t think it’s going to cure colds” or, realistically, anything else, he said.

Read: Watching tattoos go from rebellious to mainstream

Regardless of whether tattoos themselves boost immunity, they might inspire technology that does. Kobinger’s team is one of several tinkering with tattoo-needle techniques to administer shots—in ways that could make them more potent, more efficient, and easier to take. Most of the vaccines in our current roster are injected deep below the skin, into muscles, which aren’t well stocked with immune cells. The process takes time and decently large doses to truly rev up. The skin, by contrast, is “a formidable place to administer vaccines,” Kobinger told me. “The cells are already on site, and there is an immediate reaction.”

A skin-deep technique to administer vaccines already exists, called the “intradermal” route, which has been used for the shots against smallpox, tuberculosis, rabies, and recently, mpox. But intradermal vaccines require quite a bit of training to administer—and when needles miss their mark, the effectiveness of the shot can take a real nosedive.

Tattooing devices, outfitted with vaccine vials, could, in theory, circumvent those pitfalls, Kobinger said. In his experiments with various vaccines, the tattooing method has routinely outperformed the intradermal one; some, though not all, other studies have found similarly encouraging results. If the technology advances, Kobinger told me, people might someday need fewer injections of some multidose shots—saving time, money, effort, and discomfort. There’s no ink involved. But maybe these needles could still have the chance to leave permanent impressions on us.

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