RESUMO
Langerhans cell histiocytosis (LCH) is characterized by an expansion and accumulation of pathological histiocytes expressing langerin (CD207) and CD1a in different organs under an inflammatory milieu. The origin of pathognomonic precursors of LCH is widely debated, but monocytes and pre-dendritic cells (pre-DC) play a significant role. Remarkably, we found an expansion of AXLhigh cells in the CD11c+ subset of patients with active LCH, which also express the pathognomonic CD207 and CD1a. Moreover, we obtained a monocyte-derived LC-like (mo-LC-like) expressing high levels of AXL when treated with inflammatory cytokine, or plasma of patients with active disease. Intriguingly, inhibiting the mTOR pathway at the initial stages of monocyte differentiation to LC-like fosters the pathognomonic LCH program, highly increasing CD207 levels, together with NOTCH1 induction. We define here that AXLhigh could also be taken as a strong pathognomonic marker for LCH, and the release of Langerin and NOTCH1 expression depends on the inhibition of the mTOR pathway.
Assuntos
Antígenos CD , Receptor Tirosina Quinase Axl , Histiocitose de Células de Langerhans , Lectinas Tipo C , Lectinas de Ligação a Manose , Proteínas Proto-Oncogênicas , Receptores Proteína Tirosina Quinases , Serina-Treonina Quinases TOR , Feminino , Humanos , Masculino , Antígenos CD/metabolismo , Antígenos CD1/metabolismo , Biomarcadores , Diferenciação Celular , Histiocitose de Células de Langerhans/metabolismo , Lectinas Tipo C/metabolismo , Lectinas de Ligação a Manose/metabolismo , Monócitos/metabolismo , Monócitos/imunologia , Células Mieloides/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas/genética , Receptores Proteína Tirosina Quinases/metabolismo , Receptor Notch1/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/antagonistas & inibidores , Serina-Treonina Quinases TOR/metabolismoRESUMO
Dendritic cells form the link between the innate and adaptative immune response, particularly on mucosal and epidermal surfaces. The Langerhans, an epidermal dendritic cell subpopulation, play a key role in the skin immune response across several species. Scarse immune cell subpopulations, including Langerhans-like cells, have been identified in endangered green turtles thereby complicating the understanding of the pathogenesis of diseases such as fibropapillomatosis, which induces skin tumours in this species worldwide. In biopsies from green turtle skin, we demonstrated that the polyclonal anti-human Langerin antibodies strongly stained a Langerin+ cell population in epidermal sheets, the suprabasal layer of the epidermis in cryosections and in cells from cytospin preparation of migration assays. The morphology of these cells was round to amoeboid in normal skin; however, in skin with ulcerative dermatitis, Langerin+ cells aggregated around ulcers and adopted a more pleomorphic morphology. To our knowledge, this is the first identification of Langerin+ cells with a molecular marker in a reptile species.
Assuntos
Quimiocina CCL21 , Células Epidérmicas , Células de Langerhans , Tartarugas , Animais , Pele/patologia , Tartarugas/fisiologiaRESUMO
Abstract The aim of this study was to determine if the distribution of Langerhans cells (LC) and interstitial dendritic cells (IDC) is altered in AIDS-associated oral Kaposi's sarcoma when compared to HIV-negative highly vascular oral lesions. Fifty-one cases of AIDS-associated oral Kaposi's sarcoma and 20 of highly vascular oral lesions were retrospectively retrieved. All cases of Kaposi's sarcoma were confirmed with immunoreactions against CD34 and HHV-8. Clinical data regarding sex, age and lesions location were obtained from pathology reports. Immunohistochemistry against CD207 (immature dendritic cells) and CD83 (mature dendritic cells) were done. LC were in the epithelium and IDC in the stroma. CD207+ cells predominated in the epithelium of the lesions, whereas CD83+ cells predominated in their stromal compartment. Kaposi's sarcoma had a lower CD207+ immature LC count (p=0.02) and an increased CD207+ IDC than highly vascular oral lesions (p<0.001). Moreover, Kaposi's sarcoma also showed an increased number of mature CD83+ IDC than highly vascular oral lesions (p<0.001). There were significant alterations in the distribution of LC and IDC in AIDS-associated Kaposi's sarcoma when compared to HIV-negative vascular oral lesions, suggesting that changes in their concentrations may play a role in the pathogenesis of Kaposi's sarcoma.
Resumo O objetivo deste estudo foi determinar se a distribuição das células de Langerhans (CL) e das células dendríticas intersticiais (CDI) está alterada no sarcoma de Kaposi oral associado à AIDS quando comparado às lesões orais altamente vasculares HIV-negativas. 51 casos de sarcoma de Kaposi oral associado à AIDS e 20 de lesões orais altamente vasculares foram recuperados retrospectivamente. Todos os casos de sarcoma de Kaposi foram confirmados pela positividade para os anticorpos CD34 e HHV-8. Dados clínicos sobre sexo, idade e localização das lesões foram obtidos dos laudos histopatológicos. Foram realizadas imunoistoquímica contra CD207 (células dendríticas imaturas) e CD83 (células dendríticas maduras). As CL estavam presentes no epitélio enquanto as CDI estavam presentes no estroma. As células CD207+ predominaram no epitélio das lesões, enquanto as células CD83+ predominaram no estroma. O sarcoma de Kaposi teve uma contagem mais baixa de CD imaturas CD207+ (p = 0,02) e número aumentado de CDC CD207+ do que lesões orais altamente vasculares (p<0,001). Além disso, o sarcoma de Kaposi também mostrou um número aumentado de CDI CD83+ maduras do que lesões orais altamente vasculares (p<0,001). Houve alterações significativas na distribuição de CL e CDI no sarcoma de Kaposi associado à AIDS quando comparado às lesões orais vasculares HIV-negativas, sugerindo que alterações na distribuição das mesmas podem desempenhar um papel na patogênese do sarcoma de Kaposi.
Assuntos
Humanos , Sarcoma de Kaposi , Síndrome da Imunodeficiência Adquirida , Herpesvirus Humano 8 , Células Dendríticas , Estudos RetrospectivosRESUMO
Leprosy is a disease caused by Mycobacterium leprae, which is characterized by two distinct poles, the tuberculoid pole and the lepromatous pole, depending on the immune response to the bacillus. Langerin-positive cells are dendritic cells that appear to play an essential role in the development of the disease. These cells are specialized in the processing and presentation of antigens, exerting an important function in the activation of the immune system. To evaluate the expression of langerin-positive cells (CD207+) in skin lesion fragments of patients with a diagnosis of M. leprae infection and to associate the expression of these cells with the polar forms of the disease. Langerin-positive cells were detected in larger numbers in lesions of patients with the tuberculoid form compared to those with the lepromatous form. The presence of a larger number of these cells in patients with the tuberculoid form suggests an important participation of langerin-positive cells, capturing antigens and favoring an effective immune response to infection with M. leprae.
Assuntos
Antígenos CD/análise , Células Dendríticas/química , Células Dendríticas/imunologia , Lectinas Tipo C/análise , Hanseníase/patologia , Hanseníase/fisiopatologia , Lectinas de Ligação a Manose/análise , Pele/patologia , Adulto , Brasil , Feminino , Humanos , Imuno-Histoquímica , Masculino , MicroscopiaRESUMO
De novo ectopic lymphoid tissue formation is known to occur in certain disease and inflammatory settings. After an effective vaccination with dendritic cells (DC) charged with melanoma apoptotic/necrotic cells (Apo/Nec), a subcutaneous tertiary lymphoid structure was organized, where retained vaccine cells interacted with recruited inflammatory and T cells. In this work we report for the first time the recruitment of two morphologically different CD207(+) cells to vaccination site. The time-course behavior of CD207(+) cells was reciprocal between vaccination site and draining lymph nodes (DLNs). After 6-10 days, CD207(+) cells localized at the paracortical region of DLNs, in close contact with T cell population. DLNs were enriched in a peculiar MHCII(+) CD11c((-)) CD207(+) population, whose role remains to be determined. Whether CD207(+) cells migration to the vaccination site can be associated with a differential anti-tumoral response remains as an open and exciting question.