Tattoo You: Immune System Cells Help Keep Ink In Its Place

Last Saturday, while I was visiting Fatty's Tattoos and Piercings, a college-aged woman in a hoodie walked in and asked for a tattoo, her first, right on the spot.

"I want a red-tailed hawk feather," she told the artist on duty at the Washington, D.C., tattoo parlor.

He peppered her with questions: How big? What style? She alternated between a blank stare and a furrowed brow: "I ... have a photo on my phone of the feather that I like, I could show you that?"

The artist rubbed his beard and told her he didn't do realistic tattoos. Maybe they should set up an appointment for her sometime next week, with another artist, he offered. Between the lines, he seemed to say, "This will be permanent, so I don't want to give you the wrong tattoo."

But considering how many changes skin weathers — burns heal, scars fade and wrinkles set in — it's sort of unbelievable that tattoos do stick around.

Recently, a group of French scientists looked into how that works, hoping to use the knowledge to improve tattoo removal.

So, first, of course, they gave some mice tattoos.

The mice didn't get Mom tattoos on their tiny biceps. Instead, they got tail tats — three stripes of green ink — for researchers to study.

"The thing is, the mouse skin can be super fragile, much more fragile than human skin," says Sandrine Henri, an immunologist at the Centre d'Immunologie Marseille-Luminy.

If you zoom way in on any tattoo, it's really just a bunch of cells holding tight to ink particles. From the mice's tail tattoos, Henri and her colleagues identified one type of cell that captured ink particles and stayed in place, the dermal macrophage.

The researchers thought they might be able to disrupt the tattoos by destroying the macrophages that had locked up the ink. So they engineered mice whose macrophages — and only those cells — would shrivel in the face of a specific toxin, and then injected that compound into these special, tattooed mice.

But it didn't work.

The messed-up macrophages released their ink particles, but the color persisted. It turns out that new macrophages quickly took over the job of holding the tiny flecks of ink in place, and the mice kept their sporty green-striped tails.

But if it were possible, Henri says, to use an ointment, or a drug, to delay those replacement macrophages, it might improve tattoo removal for mice — and humans. The researchers' fingings appeared Tuesday in the Journal of Experimental Medicine.

To think about removing ink from human shoulders, rather than mouse tails, it helps to know how tattoos appear. In broad strokes, we understand this process, says Bruce Klitzman, a biomedical engineer at Duke who once worked on creating an erasable tattoo.

As a tattoo artist outlines a yin-yang symbol on someone's shoulder, a solid needle loaded with ink pierces the tattoo-ee's skin, or epidermis, and the needle's exit lets pigment flow into a second layer of skin, the dermis, Klitzman says.

But any self-respecting immune system treats all visitors — including the ink particles meant to create a wolf's face on your forearm — as unwelcome. So skin cells mount a multilevel attack on the ink particles.

First, the cells that weren't hit by the tattoo needle block out guests, Klitzman says. Only a fraction of the ink an artist lays down actually makes it into the dermis, and this is also why new tattoos tend to leak ink as they heal.

Newly tattooed skin swells, the same way it would respond to any other wound, and blood and lymph ferry away the smallest bits of ink. For the remaining pigment particles, the next order of the immune system's business is consuming the foreign invaders, to try to destroy them.

That's where the macrophages, the cells Henri studied, come in. They're specialized immune cells — their name means big eater in Greek — and their job is to slurp up interlopers, says Klitzman. "Macrophages can basically swallow many, many tattoo pigment particles, almost like a vacuum cleaner, just go along and suck up all those particles," he says.

Usually, a macrophage digests the invaders it devours, using acid to rip its enemy apart. It's a good strategy for killing bacteria and viruses, but not for tattoo pigments. Acid has little effect on the ink ingredients.

That means a macrophage that has gorged on ink has no way to finish its job. Eventually, the pigment-filled macrophages dial back their attack, content to contain the threat, even if they can't completely neutralize it. "They just sit there like a full vacuum cleaner bag," says Klitzman.

Another type of cell, called a fibroblast, is also known to take in some ink particles in human skin. Together, the macrophages and fibroblasts bind enough ink for the image of, say, a carrot or feather to appear on your calf.

Those cells and the pigment inside them can hang around for years. But all cells die eventually, which brought Henri and her team to their question: How do tattoos stay put as individual cells die?

Their work confirms that even when macrophages die and release their pigment particles, other macrophages quickly gobble up the ink, keeping it in place.

Even when the researchers grafted one mouse's tail tattoo onto another mouse's back, the second mouse's own macrophages carried the skin graft's tattoo. "The cells from the graft died and released the ink, and the host mouse's cells captured it," Henri says.

All of that, basically, underscores why tattoo removal is really, really difficult.

Laser removal is an option, says Jared Jagdeo, a dermatologist at University of California, Davis. Tuned to a wavelength specific to a tattoo's colors, "lasers are able to break apart tattoo particles," he says. The bursts of energy bust ink "from larger boulders into smaller rocks, and then into fine pebbles which then can be swept away by the lymphatic system."

But laser removal is far from perfect. The process of blurring ink beyond recognition can take many sessions, spaced weeks apart, at a couple hundred dollars a visit.

Laser pulses irritate skin, and people show re-uptake of ink similar to Henri's mice, Jagdeo says. He uses anti-inflammatory drugs to help tame that response, but it's really difficult to remove all evidence of a tattoo. "Tattoos are at their baseline permanent, so if [someone gets] a tattoo they should plan on having it for a while," he says.

Back at the tattoo shop, I don't know if the woman with the red-tailed hawk feather ever managed to get her tattoo. Either way, I hope she's happy with her decision. For now, tattoo removal is still a challenge.

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