RESUMO
Spirulina, an herbal supplement and popular ingredient in health foods, is a potent stimulant of the immune system. Spirulina use is temporally associated with the onset or exacerbation of Dermatomyositis (DM), an autoimmune connective tissue disease that frequently affects the skin and muscle. In this study, we investigated the effect of Spirulina on peripheral blood mononuclear cells (PBMCs) in DM and Healthy Controls (HCs), showing that Spirulina stimulates Interferon ß (IFNß), Tumor necrosis factor α (TNFα), and Interferon γ (IFNγ) production of DM PBMCs primarily via Toll-Like Receptor 4 (TLR4) activation using ELISA (enzyme linked immunosorbent assay) and flow cytometry. We show that classical monocytes and monocyte-derived dendritic cells are stimulated by Spirulina and are activated via TLR4. Skin from patients with Spirulina-associated DM exhibits an inflammatory milieu similar to that of idiopathic DM but with a stronger correlation of TLR4 and IFNγ.
RESUMO
Dermatomyositis (DM) is an autoimmune disease that affects the skin, lungs, and muscle. Although the pathogenesis of DM is not completely understood, several environmental triggers have been linked to DM onset or flare. This article specifically examines the effects of herbal supplements, drugs, infections, ultraviolet (UV) radiation, and environmental pollutants on the onset or exacerbation of DM. Herbal supplements such as Spirulina platensis, Aphanizomenon flos-aquae, Chlorella, Echinacea, and Alfalfa have been implicated and are frequently used in health foods. Medications such as hydroxyurea, TNF-α inhibitors, immune checkpoint inhibitors (ICI), and penicillamine, as well as certain viral infections, such as parvovirus B19, coxsackie virus, polyomavirus, Epstein-Barr virus (EBV), hepatitis, influenza, and human immunodeficiency viruses (HIV) have been associated with DM onset. Bacterial infections and vaccinations have also been linked to the development of DM. Additional environmental factors, including UV radiation and air pollutants, such as silica, biological/mineral dust, and particulate air matter from vehicle and industrial emissions, may also play a role in DM pathogenesis. Overall, there is general agreement that an autoimmune attack of the skin, muscle, and lungs in DM can be triggered by various environmental factors and warrants further investigation.
RESUMO
Dermatomyositis (DM) is a rare, systemic autoimmune disease that most frequently affects the skin, muscles, and lungs. The inflammatory infiltrate in the skin has not been fully characterized, and, in this study, we took a single-cell, unbiased approach using imaging mass cytometry. Substantial monocyteâmacrophage diversity was observed, with the CD14+ population correlating positively with Cutaneous Dermatomyositis Disease Area and Severity Index scores (P = 0.031). The T-cell compartment revealed CD4+ T, CD8+ T, and FOXP3+ T cells. Activated (CD69+) circulating memory T cells correlated positively with Cutaneous Dermatomyositis Disease Area and Severity Index scores (P = 0.0268). IFN-ß protein was highly upregulated in the T-cell, macrophage, dendritic cell, and endothelial cell populations of DM skin. Myeloid dendritic cells expressed phosphorylated peroxisome proliferatorâactivated receptor γ, phosphorylated IRF3, IL-4, and IL-31, and their quantity correlated with itch as measured in Skindex-29. Plasmacytoid dendritic cells colocalized with IFN-γ in addition to the known colocalization with IFN-ß. Nuclear phosphorylated peroxisome proliferatorâactivated receptor γ expression was found in the DM endothelium. Imaging mass cytometry allows us to characterize single cells in the immune cell population and identify upregulated cytokines and inflammatory pathways in DM. These findings have important implications for the development of future targeted therapies for DM.
Assuntos
Células Dendríticas/imunologia , Dermatomiosite/imunologia , Endotélio/metabolismo , Macrófagos/imunologia , Pele/imunologia , Subpopulações de Linfócitos T/imunologia , Linfócitos T Reguladores/imunologia , Células Cultivadas , Citocinas/metabolismo , Endotélio/patologia , Fatores de Transcrição Forkhead/metabolismo , Humanos , Memória Imunológica , Imunofenotipagem , Fator Regulador 3 de Interferon/metabolismo , Receptores de Lipopolissacarídeos/metabolismo , PPAR gama/genética , PPAR gama/metabolismoRESUMO
Today, parents are warned to protect their children from the sun's ultraviolet (UV) rays, the most preventable and leading cause of skin cancer. Yet, during the first half of the 20th century, the medical community widely extolled the health benefits of daily sunbaths for babies and children. What initially had begun as evidence-based medical therapies to prevent pediatric diseases, specifically tuberculosis and rickets, soon took on a life of its own as physicians, public health experts, and the general public embraced sunbathing and tanning as a means to ensure health and wellbeing for children and families. Here, we trace how specific medical therapies entered mainstream pediatric medicine and, converging with societal and cultural forces, shaped attitudes and behaviors towards sunbathing that still exist today. Understanding our complex history with the sun may shed light on the current peak of skin cancer incidence and future disease development. Moreover, it may help improve how we educate parents and children about sun safety by taking into account the current social and cultural context of medical practice and health communication.