Commentary on 'Sebocyte differentiation as a new target for acne therapy: an in vivo experience'

This article is a commentary on the paper by Ottaviani et al. ‘Sebocytedifferentiation as a new target for acne therapy: an in vivo experience’. (Ottaviani M, Flori E, Mastrofrancesco A et al. Sebocyte differentiation as anew target for acne therapy: an in vivo experience. J Eur Acad DermatolVenereol 2020; 34: 1803–1814. doi: 10.1111/jdv.16252.

Deletion series in the P1 protein of the Sweet potato mild mottle virus identifies the shortest fully functional RNA silencing suppressor domain

RNA silencing is a part of the plant innate immune system that could effectively cope with intruders, like viruses. However, viruses evolved proteins that can suppress RNA silencing thus supporting virus spreading in the host. To counteract RNA silencing, suppressor proteins attack different players of RNA silencing pathway. The P1 protein of the Sweet potato mild mottle virus binds and inactivates small RNA loaded RISC complexes. Using a deletion series in the P1 protein we aimed to identify the possible smallest working version of P1. Our results revealed that the minimal RNA silencing suppressor domain of P1 is as small as 210 amino acids in size

A hámsejtek immunológiai működésében résztvevő gének azonosítása DNS-microarray módszerrel = Identification of genes involved in the immune-function of epithelial cells using DNA microarray.

A hámsejtek immunológiai működésében résztvevő gének azonosítása DNS-microarray módszerrel Az emberi szervezetet a külső környezettől elválasztó legfontosabb határoló szervünk a bőr, amely egyrészt mechanikai védelmet nyújt a külvilág káros hatásai ellen, másrészt aktív, protektív feladatokat is ellát. Munkacsoportunk a bőrnek és a hámsejteknek a veleszületett immunitásban betöltött szerepét kutatja. Vizsgálataink során cDNS microarray módszerrel vizsgáltuk azt a kérdést, hogy a különféle bakteriális és gomba eredetű anyagok (LPS, PGN, hővel elölt Candida albicans, élő Propionibacterium acnes) milyen génexpresszós változásokat okoznak primer tenyésztett keratinocitákban. Eredményeink alapján igazoltuk, hogy a keratinocitákban gyulladásos citokin, kemokin, és antimikrobiális hatású fehérjét kódoló gének kifejeződése megváltozik a patogén eredetű anyagok hatására. A folyamatok szabályozásában a Toll-like receptorok, valamint NF-kB játszik központi szerepet. Igazoltuk, hogy a patogének támadásának kitett testfelületeken számos nem immun-eredetű sejttípus rendelkezik a kórokozók felismerésének képességével, ezek bakteriális és gomba-eredetű anyagok hatására képesek a veleszületett és adaptív immunfolyamatok elindítására és szabályozására. Eredményeink elméleti jelentősége mellett egy olyan tesztrendszer bevezetését is lehetővé tették, mely alkalmas gyulladásos bőrbetegségek esetén alkalmazott lokális immunmoduláló szerek hatásmechanizmusának vizsgálatára. | Identification of genes involved in the immune-function of epithelial cells using DNA microarray. The human skin is the most important barrier of the organism. It can not only passively separate the outer environment from the inner body, but also plays an active protective function. Our main focus is the better understanding of the innate immune functions of epidermal keratinocytes. For this reason we have investigated the global gene expression changes in response to various microbial components (PLS, PGN, heat-killed Candida albicans, and live Propionibacterium acnes) in primary keratinocytes using the microarray technique. Based on our results we could show, that the expression of various pro-inflammatory cytokine, chemokine, and antimicrobial peptide coding genes are changing in response to pathogen derived chemical compounds, and whole pathogen cells. Toll-like receptors and NF-kB are playing an important role in the regulation of these genes. Our results also suggest, that this ability of the keratinocytes is not unique to them, other cell types on various surfaces of the body where pathogen attack happens regularly can also recognize the microbes and initiate and regulate immune processes. Based on our data, we also set up an experimental model system that can be used for the evaluation of the exact function of various topical immunmodulatory chemicals used to treat inflammatory skin diseases

Melanoma Cells Can Adopt the Phenotype of Stromal Fibroblasts and Macrophages by Spontaneous Cell Fusion in Vitro

After the removal of primary cutaneous melanoma some patients develop local recurrences, even after having histologically tumor-free re-excision. A potential explanation behind this phenomenon is that tumor cells switch their phenotype, making their recognition via standard histopathological assessments extremely difficult. Tumor-stromal cell fusion has been proposed as a potential mechanism for tumor cells to acquire mesenchymal traits; therefore, we hypothesized that melanoma cells could acquire fibroblast- and macrophage-like phenotypes via cell fusion. We show that melanoma cells spontaneously fuse with human dermal fibroblasts and human peripheral blood monocytes in vitro. The hybrid cells' nuclei contain chromosomes from both parental cells and are indistinguishable from the parental fibroblasts or macrophages based on their morphology and immunophenotype, as they could lose the melanoma specific MART1 marker, but express the fibroblast marker smooth muscle actin or the macrophage marker CD68. Our results suggest that, by spontaneous cell fusion in vitro, tumor cells can adopt the morphology and immunophenotype of stromal cells while still carrying oncogenic, tumor-derived genetic information. Therefore, melanoma-stromal cell fusion might play a role in missing tumor cells by routine histopathological assessments

Melanoma-Derived BRAF(V600E) Mutation in Peritumoral Stromal Cells: Implications for in Vivo Cell Fusion

Melanoma often recurs in patients after the removal of the primary tumor, suggesting the presence of recurrent tumor-initiating cells that are undetectable using standard diagnostic methods. As cell fusion has been implicated to facilitate the alteration of a cell's phenotype, we hypothesized that cells in the peritumoral stroma having a stromal phenotype that initiate recurrent tumors might originate from the fusion of tumor and stromal cells. Here, we show that in patients with BRAF(V600E) melanoma, melanoma antigen recognized by T-cells (MART1)-negative peritumoral stromal cells express BRAF(V600E) protein. To confirm the presence of the oncogene at the genetic level, peritumoral stromal cells were microdissected and screened for the presence of BRAF(V600E) with a mutation-specific polymerase chain reaction. Interestingly, cells carrying the BRAF(V600E) mutation were not only found among cells surrounding the primary tumor but were also present in the stroma of melanoma metastases as well as in a histologically tumor-free re-excision sample from a patient who subsequently developed a local recurrence. We did not detect any BRAF(V600E) mutation or protein in the peritumoral stroma of BRAF(WT) melanoma. Therefore, our results suggest that peritumoral stromal cells contain melanoma-derived oncogenic information, potentially as a result of cell fusion. These hybrid cells display the phenotype of stromal cells and are therefore undetectable using routine histological assessments. Our results highlight the importance of genetic analyses and the application of mutation-specific antibodies in the identification of potentially recurrent-tumor-initiating cells, which may help better predict patient survival and disease outcome