Tattoo ink alters immune cells and weakens some vaccine responses

New research reveals that tattoo pigments don’t just stay in the skin, they migrate into lymph nodes, trigger months of inflammation, and reshape how the body responds to different vaccines.

In a recent study published in PNAS, researchers investigated the journey of tattoo ink through the lymphatic system as it accumulates in lymph nodes and affects immune cells, examining its long-term effects on immune responses to vaccination.

They demonstrated that tattoo ink rapidly drains to lymph nodes, where macrophages take it up and often undergo cell death, triggering persistent inflammation for months. These effects were observed when vaccination occurred in the same lymphatic drainage area as the tattoo. Ink accumulation reduced immunity to messenger ribonucleic acid (mRNA) vaccines for the coronavirus disease 2019 (COVID-19) when administered at the tattoo site, but enhanced responses to an influenza vaccine in an ink- and timing-dependent manner.

Long-term behavior of tattoo ink

Tattooing has become highly prevalent worldwide, particularly among younger populations, with around 20 % of people globally and over 30 % in the United States having at least one tattoo.

The process introduces pigments deep into the dermis through repeated needle penetration. Because these pigments are designed to be insoluble and long-lasting, they often contain complex mixtures of binders, solvents, and industrial colorants.

While black tattoos typically use carbon black, colored inks commonly contain pigments originally designed for industrial applications such as plastics and paints. Despite widespread use, tattoo inks are far less regulated than pharmaceuticals or other substances intentionally introduced into the body. Although some toxicology data exist for individual ingredients, little is known about how inks behave inside living systems, especially over the long term.

Macrophages in the skin are known to engulf tattoo pigments, and tattoo-related pigment deposits have been reported in lymph nodes for decades. Mouse studies confirm that ink drains from the skin into lymph nodes, yet the immunological consequences of this process are poorly understood.

Ink toxicity in mouse and human macrophages

Researchers used a mouse footpad tattoo model to study the behavior of commercial black, red, and green inks after injection. After ensuring the inks met European chemical safety standards, they tattooed a small area and employed electron microscopy to confirm the presence of ink throughout the epidermis and dermis.

They then performed intravital imaging to track the movement of ink through lymphatic vessels shortly after tattooing. Lymph nodes were examined multiple times over a period of up to two months using confocal microscopy to map pigment distribution across different lymph node regions, including subcapsular, medullary, and paracortical areas.

To identify which immune cells internalized the pigments, the researchers stained lymph node tissue for macrophage and dendritic cell markers, quantifying colocalization of ink with specific cell types.

Transmission electron microscopy provided ultrastructural confirmation of pigment-filled phagocytic cells and giant cell formation. To assess macrophage viability, they used both in vivo cell counts and in vitro assays. Bone-marrow–derived and human blood–derived macrophages were exposed to different ink dilutions, and cell death was measured using propidium iodide staining, apoptosis markers, and flow cytometry.

Finally, vaccine-response experiments evaluated how ink-filled lymph nodes affected antibody production following either an mRNA COVID-19 vaccine or an influenza vaccine.

Ink floods lymph nodes and kills macrophages over time

All tested inks drained rapidly through lymphatic vessels, reaching peak levels within minutes and accumulating primarily in the popliteal lymph node within 24 hours. Some ink continued to spread to downstream nodes.

Early staining revealed that pigment was concentrated in the subcapsular and medullary regions; by two months, pigment levels had increased further and extended into deeper lymph node areas. Human lymph node biopsies displayed similar patterns, indicating that these findings are likely to translate to humans at least in terms of pigment deposition and macrophage involvement.

Macrophages were the primary cells that captured and retained pigments, far more so than dendritic cells or other phagocytes. Electron microscopy confirmed that macrophages were packed with pigment-filled vacuoles, along with the formation of giant cells over time. Many pigment-containing macrophages showed structural signs of distress, such as membrane disruption and blebbing.

Correspondingly, in vivo macrophage numbers first rose and then declined sharply shortly after tattooing, suggesting cell death. In vitro assays confirmed concentration-dependent ink uptake and demonstrated that all inks triggered apoptosis or necrosis in mouse and human macrophages, though the timing varied by ink color.

Tattooing also induced strong and persistent lymph node inflammation, characterized by increased total cell numbers and inflammatory immune-cell recruitment. Importantly, ink-filled lymph nodes draining the tattoo site changed subsequent vaccine responses. Antibody production was reduced after the mRNA COVID-19 vaccine, only when vaccination occurred in the same tattoo-draining area. In contrast, influenza vaccine responses were enhanced, with black and especially red inks boosting certain antibody responses depending on whether vaccination occurred shortly after tattooing or two months later.

Long-lasting pigment buildup may alter immune health

Tattoo ink was shown to drain quickly into lymph nodes, accumulate over time, and persist for months in mice, raising concerns about long-term pigment buildup in people with large or multiple tattoos in a body region. The study found that ink-laden macrophages often undergo cell death, potentially weakening lymph node antimicrobial functions and altering inflammatory pathways.

Chronic inflammation and pigment-specific toxicity, particularly from red and black inks, may contribute to broader health risks, including impaired vaccine responses in the affected lymphatic region and potentially increased cancer susceptibility. However, the latter remains speculative and requires further human research.

A key strength is the comprehensive analysis of multiple ink types and immune outcomes; however, the findings are limited because the vaccine experiments were conducted in mice. The authors emphasize that more clinical studies are needed, despite supportive human ex vivo data. Overall, the study highlights significant gaps in tattoo-ink regulation and urges further research on systemic and immunological impacts.

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Journal reference:

• Capucetti, A., Falivene, J., Pizzichetti, C., Latino, I., Mazzucchelli, L., Schacht, V., Hauri, U., Raimondi, A., Virgilio, T., Pulfer, A., Mosole, S., Grau-Roma, L., Bäumler, W., Palus, M., Renner, L., Ruzek, D., Levy, G.G., Foerster, M., Chahine, K., Gonzalez, S.F. (2025). PNAS 122(48): e2510392122. DOI: 10.1073/pnas.2510392122. https://www.pnas.org/doi/10.1073/pnas.2510392122