Immune responses to tattoos

More and more, tattoos are becoming more common; however, this trend has raised security concerns. There are toxicological and biokinetic considerations to be made when it comes to tattoos. However, animal testing that is necessary to address these safety issues is considered unethical because, like cosmetics, it has no medical necessity.

Tattoo. Image credit: Olena Yakobchuk/

Among these safety issues are those related to the immune system. Indeed, tattooing involves the insertion of ink into tiny perforations created in the epidermis, and the pigments are considered a foreign body capable of triggering the immune response.

How does the tattoo work?

Tattoos are permanent deposits of insoluble pigments in the dermal layer of the skin. Once tattoo inks are injected into the skin, the ink particles can either be passively transported via blood and lymphatic fluids or subjected to phagocytosis by immune cells, after which they settle in the lymph nodes. Once healing is complete, the dermis contains particles – just like the sinusoids of the draining lymph nodes.

What is tattoo pigment made of?

Tattoo pigments consist of either inorganic metals and their oxides or polyaromatic compounds; all of these are considered biologically inert. These metals include nickel, chromium, manganese and cobalt. Besides carbon black, the most commonly used ingredient is titanium dioxide. It is a white pigment that is used to create shades when mixed with other colored compounds. The toxicity of titanium dioxide depends on its crystal structure, the photocatalytically active anatase structure, which can produce reactive oxygen species when exposed to daylight.

According to a 2017 article published in the journal Scientific Reports, there is analytical evidence to support the transport of organic and inorganic pigments, alongside impurities of toxic elements in tattoo ink – which eventually reach the lymph nodes. Scientists at the European Synchrotron Radiation Facility (ESRF) in Grenoble, France, performed X-ray fluorescence measurements to identify locations of titanium dioxide in the micro and nano range of the skin and lymphatic system.

The researchers observed the transport of organic pigments, heavy metals and titanium dioxide from the injection site to the regional lymph nodes. Organic pigments showed the largest size range, with the smallest (nano) particles reaching the lymph nodes.

In addition to the migration changes, the researchers were able to detect changes in the structure of the tissues adjacent to the tattoo particles. This was mediated by altered ratios between amide I α-helix and β-sheet protein and increased lipid content.

Taken together, the authors reported strong evidence for both migration and long-term deposition of tattoo pigment, as well as conformational alteration of biomolecules that can cause skin inflammation and other adverse effects due to tattooing. tattoo.

Tattoos and the Immune Response – Maintaining Tattoos Long-Term

The dermis layer of the skin, the site on which tattoo ink is deposited, is rich in blood vessels, lymph vessels, nerves and other structures. In the dermis, there are dermal dendritic cells, macrophages, CD4+ T cells and innate lymphoid cells. These cells are well positioned to react in response to damage, such as that caused by a tattoo needle penetrating the skin to inject pigment. The pigment in the ink is considered a foreign body, which provokes an immune response to try to eliminate it.

The newly tattooed skin swells and, although the majority remains at the deposition site in the dermis, regional lymph node migration is observed, as noted above.

When tattoo ink lingers in the skin, dermal macrophages engulf the ink. The ink is sequestered in their vacuoles. The enzymes present in the vacuole are not able to break down the ink. According to a 2018 study, researchers determined the origin, identity, and dynamics of the myeloid skin cells that are responsible for capturing and retaining these tattoo pigment particles.

These researchers demonstrated that these myeloid cells are exclusively made up of dermal macrophages and not of resident dermal cells. That is, other cell types play no role in the containment of the pigment that is injected into the dermal layer. Additionally, deletion analysis demonstrated that tattoo pigment particles are able to undergo capture-release-recapture cycles without the risk of losing the tattoo at the injection site.

The researchers used diphtheria toxin to selectively kill cells expressing CD64, a monocyte marker. CD64 is expressed on monocytes, macrophages, myeloid cell precursors and follicular dendritic cells. Through the generation of mice engineered to have the diphtheria receptor under the control of the CD64 gene, all myeloid cells were specifically targeted for ablation (i.e. deletion).

The researchers found that the death of macrophages results in the release of the trapped pigment; however, two days after treatment with diphtheria toxin, the macrophage pool is replenished by circulating macrophages, which in turn have been replenished by bone marrow-derived monocytes. These near-derived macrophages then engulf the free ink released by the earlier macrophage population – and this process continues indefinitely, ensuring the permanence of the tattoos.

Therefore, the researchers concluded that the long-term persistence of tattoos depends on macrophage turnover rather than macrophage longevity.

Tattoo processTattoo process. Image Credit: Designua/

The Role of Tattoos in Immune Boosting

A study published in 2016 measured immune function using secretory immunoglobulin A (SIgA) and cortisol found in the saliva of 29 participants to investigate the “inoculation hypothesis” of tattooing. This inoculation hypothesis suggests that tattooing inoculates the immune system, inducing increased protection against stressors that damage soft tissue.

Tattooing experience was measured as the sum of the number of tattoos, lifetime hours tattooed, number of years since participants’ first tattoo, percentage of body covered, and number of tattoo sessions.

The researchers observed an inverse relationship between SIgA and cortisol, with less immunosuppression of SIgA in those with more tattoo experience. Those without pre-existing tattoos experienced a greater strain on their immune system, observed by a greater drop in their SIgA.

Taken together, the data suggests that the body gets used to the external insult of tattooing over time. Importantly, however, the authors noted that people with a healthy immune system heal faster, which increases their likelihood of a subsequent tattoo experience.


  • Baranska A, Shawket A, Jouve M, et al. The unveiling of the dynamics of cutaneous macrophages explains both the persistence of the tattoo and its intense elimination. J Exp Med. 2018;215(4):1115-1133. doi:10.1084/jem.20171608.
  • Lynn CD, Dominguez JT, DeCaro JA. The tattoo to “toughen up”: Experience of tattooing and secretory immunoglobulin A. Am J Hum Biol. 2016;28(5):603-9. doi: 10.1002/ajhb.22847.
  • Schreiver I, Hesse B, Seim C, et al. Synchrotron-based ν-XRF mapping and μ-FTIR microscopy are used to study the fate and effects of tattoo pigments on human skin. Sci Rep. 2017;7(1):11395. doi:10.1038/s41598-017-11721-z

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