Conventional dendritic cells (cDCs) are immune cells, which upon stimulation from an outside invader, rush to nearby lymph node to initiate adaptive immune responses. cDCs tend to have a limited lifespan, therefore they are continuously replenished within the bone marrow, however, under homeostatic conditions these monocytes slowly invade non-lymphatic tissues. Once within a non-lymphatic tissue, such as skin dermis, the monocytes develop further into monocyte derived dendritic cells (mo-DCs) or tissue-resident macrophages (mo-Mac). These Mo-Macs eventually completely replace the natural pool of macrophages present in certain non-lymphatic tissues, such as in the intestine and dermis. Normally, macrophages are responsible for phagocytic destruction of toxic materials, such as cellular debris, foreign organisms, apoptotic cells, or even self-made particles. Macrophages which are responsible for ingesting these “self-made” debris are called melanin-laden macrophages or melanophages because they have a tendency to ingest debris from the human dermis. In order to further analyze the specialized activity of individual immune cell types, researchers developed mice which expressed the human diphtheria toxin (hDTR) under the control of the CD64 gene (high affinity IgG receptor) to selectively kill off mo-DCs and mo-Macs found in non-lymphatic tissue. These mice seemed to have a significantly high percentage of melanophages within their dermis compared with other myeloid cells that were not able to be identified in previous studies. Interestingly, the researchers identified that these cells seemed to have a high rate of ingesting melanin granules. Specifically, these cells were able to consume tissue-derived pigment particles, digest, and recycle them for continuous ingestion from other melanocytes without any negative effect on the tattoo. Therefore, they concluded that the continuous renewal of pigment ingesting macrophages is responsible for tattoo longevity, not necessarily the long life span of the macrophages themselves.
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