THE ROLE OF MACROPHAGES IN THE RETENTION AND TRANSFORMATION OF PIGMENT IN THE SKIN – THE IMMUNOLOGY OF TATTOOS
Abstract
Tattooing involves intradermal deposition of pigment that elicits a long‑lasting immune response. Dermal macrophages play a key role in maintaining pigment by capturing pigment particles and retaining them inside their phagolysosomes. The aim of this paper is to analyze the mechanisms of phagocytosis of tattoo pigment by dermal macrophages, their impact on tattoo persistence, and to assess the significance of phenotypic differentiation (M1/M2) in the context of inflammation, laser therapy, and potential biomedical applications. We reviewed data from recent experimental studies, including 3D skin models, electron microscopy, flow cytometry, and TPE‑FLIM imaging. We also considered the effect of pigment chemical composition on activation of immune cells. Dermal macrophages demonstrate high efficiency in phagocytosis and long‑term storage of pigment. The observed “capture–release–recapture” mechanism ensures pigment stability despite natural cellular turnover. Pigment composition influences macrophage polarization (M1 or M2), which may determine chronic inflammation versus regeneration. Understanding macrophage–pigment dynamics provides new insights into tattoo durability and opens opportunities to improve the effectiveness of laser removal. Advances in imaging and the use of biosensor cells point to potential future applications of tattoos in diagnostic and regenerative medicine.
References
Deter‑Wolf, A., Robitaille, B., Krutak, L., & Galliot, S. (2016). The world’s oldest tattoos. Journal of Archaeological Science: Reports, 5, 19–24.
Fisher, J. A. (2002). Tattooing the body, marking culture. Body & Society, 8(4), 91–107. https://doi.org/10.1177/1357034X02008004005
Krutak, L. F. (2012). Spiritual skin: magical tattoos and scarification: Wisdom, healing, shamanic power, protection. Ed. Reuss.
Caplan, J. (Ed.). (2000). Written on the body: The tattoo in European and American history. Princeton University Press.
Vail, D. A., Sanders, C. (2009). Customizing the Body: The Art and Culture of Tattooing. Temple University Press.
Alker, Z., Shoemaker, R. Convicts and the Cultural Significance of Tattooing in Nineteenth‑Century Britain. Journal of British Studies 2022;61(4):835–862. https://doi.10.1017/jbr.2022.117
DeMello, M. (2000). Bodies of inscription: A cultural history of the modern tattoo community. Duke University Press.
Pitts, V. (2003). In the flesh: The cultural politics of body modification. Springer.
Atkinson, M. (2003). Tattooed: The sociogenesis of a body art. University of Toronto Press.
Barańska, A., Shawket, A., Jouve, M., Baratin, M., Malosse, C., Voluzan, O., ... & Malissen, B. (2018). Unveiling skin macrophage dynamics explains both tattoo persistence and strenuous removal. Journal of Experimental Medicine, 215(4), 1115–1133. https://doi.10.1084/jem.20171005
Lin, C., Marquardt, Y., Rütten, S. et al. Macrophage‑like rapid uptake and toxicity of tattoo ink in human monocytes. Immunology. 2023;171(3):388–401. https://doi.10.1111/imm.13714
Sleth, J. C. Epidural anaesthesia and lumbar tattoo. Histology of tattoo: The missing link? Ann Fr Anesth Reanim. 2007;26(3):266–267. https://doi.10.1016/j.annfar.2006.11.007
Kaplan, D. H. Langerhans cells: not your average dendritic cell. Trends Immunol. 2017;38(11):798–808. https://doi.10.1016/j.it.2017.07.006
Tamoutounour, S. et al. Origins and functional specialization of macrophages and of conventional and monocyte‑derived dendritic cells in mouse skin. Immunity. 2013;39(5):925–938. https://doi.10.1016/j.immuni.2013.10.004
Rittig, S. M. et al. Skin immunology: macrophages in the dermis originate from yolk sac progenitors and maintain themselves through local proliferation. Pflügers Archiv – European Journal of Physiology. 2017;469(3–4):527–536. https://doi.10.1007/s00424-017-1986-1
Devčić, J., Dussol, B., Collin‑Faure, V. et al. Immediate and sustained effects of cobalt‑ and zinc‑containing pigments on macrophages. Front Immunol. 2022;13:865239. doi:10.3389/fimmu.2022.865239
Lin, C., Marquardt, Y., Rütten, S. et al. Macrophage‑like rapid uptake and toxicity of tattoo ink in human monocytes. Immunology. 2024;171(3):388–401. https://doi.10.1111/imm.13714
Strandt, H., Voluzan, O., Niedermair, T., Ritter, U., Thalhamer, J., Malissen, B., Stoecklinger, A., Henri. Macrophages and Fibroblasts Differentially Contribute to Tattoo Stability. Dermatology. 2021;237(2):296–302. https://doi.10.1159/000506540
Kröger, M., Schleusener, J., Lademann, J., Meinke, M. C., Jung, S., Darvin, M. E. Tattoo pigments are localized intracellularly in the epidermis and dermis of fresh and old tattoos: In vivo study using two‑photon excited fluorescence lifetime imaging. Dermatology. 2023;239(3):478–493. https://doi.10.1159/000529577
Barua, S. Laser‑tissue interaction in tattoo removal by Q‑switched lasers. J Cutan Aesthet Surg. 2015;8(1):5–8. https://doi.10.4103/0974-2077.155063
Bäumler, W. Laser Treatment of Tattoos: Basic Principles. Curr Probl Dermatol. 2017;52:94–104. https://doi.10.1159/000450809
Du, X. J., Zhou, H. M., Wang, Z., Liu, J., Wang, J. F., Li, D., Wu, T. T., Chen, B., Zeng, W. H. Comparative study of 1064 nm nanosecond, 1064 nm picosecond, 755 nm, and 595 nm lasers for tattoo removal: An essential role by macrophage. Lasers Surg Med. 2022;54(5):737–746. https://doi.10.1002/lsm.23535
Malca, N., Boulart, L., Noël, W., de Runz, A., Chaouat, M., Mimoun, M., Boccara, D. The adjuvant use of macrophage colony‑stimulating factor in tattoo removal using laser surgery. Ann Chir Plast Esthet. 2017;62(2):e15–e21. https://doi.10.1016/j.anplas.2016.09.005
Tastanova, A., Folcher, M., Müller, M., Camenisch, G., Ponti, A., Horn, T., ... & Fussenegger, M. (2018). Synthetic biology‑based cellular biomedical tattoo for detection of hypercalcemia associated with cancer. Science Translational Medicine, 10(437). https://doi.10.1126/scitranslmed.aap856
Allen, M. E., Kamilova, E., Monck, C., Ceroni, F., Hu, Y., Yetisen, A. K., Elani, Y. Engineered bacteria as living biosensors in dermal tattoos. Adv Sci (Weinh). 2024;11(30):e2309509. https://doi.10.1002/advs.202309509
He, R., Liu, H., Fang, T., Niu, Y., Zhang, H., Han, F., Gao, B., Li, F., Xu, F. A colorimetric dermal tattoo biosensor fabricated by microneedle patch for multiplexed detection of health‑related biomarkers. Adv Sci (Weinh). 2021;8(24):e2103030. https://doi.10.1002/advs.202103030
Debnath, S., Agrawal, A., Jain, N., Chatterjee, K., & Player, D. J. (2025). Collagen as a bio‑ink for 3D printing: A critical review. Journal of Materials Chemistry B, 13, 1890–1919. https://doi.org/10.1039/D4TB01060D
Burns, N., Rajesh, A., Manjula‑Basavanna, A., & Duraj‑Thatte, A. (2025). 3D extrusion bioprinting of microbial inks for biomedical applications. Advanced Drug Delivery Reviews, 217, 115505. https://doi.org/10.1016/j.addr.2024.115505
Byrne, R., Carrico, A., Lettieri, M., Rajan, A. K., Forster, R. J., & Cumba, L. R. (2024). Bioinks and biofabrication techniques for biosensors development: A review. Materials Today Bio, 28, 101185. https://doi.org/10.1016/j.mtbio.2024.101185
Views:
38
Downloads:
14
Copyright (c) 2025 Amelia Kosowska, Michalina Kosowska, Marlena Radzka, Izabela Radzka, Justyna Jankowska, Jonatan Rataj, Kamil Harenza, Karolina Sara Ollik, Magdalena Barbara Kukulska, Michał Kowalczyk
This work is licensed under a Creative Commons Attribution 4.0 International License.
All articles are published in open-access and licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). Hence, authors retain copyright to the content of the articles.
CC BY 4.0 License allows content to be copied, adapted, displayed, distributed, re-published or otherwise re-used for any purpose including for adaptation and commercial use provided the content is attributed.
