Dendritic cells drive profibrotic inflammation and aberrant T cell polarization in systemic sclerosis.

OBJECTIVES: SSc is a devastating autoimmune disease characterized by fibrosis and obliterative vasculopathy affecting the skin and visceral organs. While the processes mediating excessive extracellular matrix deposition and fibroblast proliferation are clear, the exact link between autoimmunity and fibrosis remains elusive. Th17 cells have been proposed as critical drivers of profibrotic inflammation during SSc, but little is known about the immune components supporting their pathogenic role. Our aim was to determine cytokine responses of stimulated monocyte-derived dendritic cells (Mo-DCs) and to determine how they influence T-cell cytokine production in SSc. MATERIAL AND METHODS: Dendritic cells (DCs) activate and shape T cell differentiation by producing polarizing cytokines. Hence, we investigated the cytokine responses of monocyte-derived DCs (Mo-DCs) from patients with limited cutaneous SSc (lcSSc), diffuse cutaneous SSc (dcSSc) and healthy controls (HCs) after stimulation with toll-like receptor (TLR) agonists. Also, using co-culture assays, we analysed T cell subpopulations after contact with autologous TLR-activated Mo-DCs. RESULTS: In general, we observed an increased production of Th17-related cytokines like IL-1ß, IL-17F, IL-21 and IL-22 by SSc compared with HC Mo-DCs, with variations between lcSSc vs dcSSc and early- vs late-stage subgroups. Noticeably, we found a significant increment in IL-33 production by Mo-DCs in all SSc cases regardless of their clinical phenotype. Strikingly, T cells displayed Th2, Th17 and dual Th2-Th17 phenotypes after exposure to autologous TLR-stimulated Mo-DCs from SSc patients but not HCs. These changes were pronounced in individuals with early-stage dcSSc and less significant in the late-stage lcSSc subgroup. CONCLUSIONS: Our findings suggest that functional alterations of DCs promote immune mechanisms favouring the aberrant T cell polarization and profibrotic inflammation behind clinical SSc heterogeneity.

Keratinocyte Response to Infection with Sporothrix schenckii.

Sporotrichosis is a subacute, or chronic mycosis caused by traumatic inoculation of material contaminated with the fungus Sporothrix schenckii which is part of the Sporothrix spp. complex. The infection is limited to the skin, although its progression to more severe systemic or disseminated forms remains possible. Skin is the tissue that comes into contact with Sporothrix first, and the role of various cell lines has been described with regard to infection control. However, there is little information on the response of keratinocytes. In this study, we used the human keratinocyte cell line (HaCaT) and evaluated different aspects of infection from modifications in the cytoskeleton to the expression of molecules of the innate response during infection with conidia and yeast cells of Sporothrix schenckii. We found that during infection with both phases of the fungus, alterations of the actin cytoskeleton, formation of membrane protuberances, and loss of stress fibers were induced. We also observed an overexpression of the surface receptors MR, TLR6, CR3 and TLR2. Cytokine analysis showed that both phases of the fungus induced the production of elevated levels of the chemokines MCP-1 and IL-8, and proinflammatory cytokines IFN-α, IFN-γ and IL-6. In contrast, TNF-α production was significant only with conidial infection. In late post-infection, cytokine production was observed with immunoregulatory activity, IL-10, and growth factors, G-CSF and GM-CSF. In conclusion, infection of keratinocytes with conidia and yeast cells of Sporothrix schenckii induces an inflammatory response and rearrangements of the cytoskeleton.

Anthropometric measure and adipokine levels of a young undergraduate population with a usual diet.

INTRODUCTION: Background: the aim of this study was to evaluate the intake of nutrients, anthropometric parameters, health indicators, adipokines and insulin levels in a population of young undergraduates. Method: in this study, 378 young undergraduates were invited to participate. Due to the inclusion criteria and their own decision of participating, 90 attended the anthropometric, health indicators: waist circumference (WC), waist to hip ratio (WHR), waist to height ratio (WHtR), and homeostatic model assessment-insulin resistance index (HOMA-IR) studies and completed the questionnaire of frequency of food intake; and 34 participants were selected to perform the determination of biochemical parameters, insulin and adipokines levels: leptin, IL-6, IL-8, tumor necrosis factor alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1) and hepatocyte growth factor (HGF). Results: according to WC, WHR and WHtR, obese population showed health, cardiovascular and metabolic risk. Overweight population showed cardiometabolic risk. In general, lipid intake was higher than 30%, being animal fat the most consumed. The levels of leptin (women: 17.2 ± 9.2, 28 ± 11.3, 36.8 ± 17.8; men: 4.3 ± 3.6, 9.5 ± 3.1, 24.6 ± 16.4 to lean overweight and obese, respectively) and insulin (women: 408 ± 182, 438 ± 187, 768 ± 167; men: 244 ± 88, 520 ± 256, 853 ± 590) increased along with body mass index (BMI), body fat percentage (BFP), visceral fat area (VFA), WC, WHR and WHtR. Lean (2.4 ± 1.3), overweight (2.2 ± 0.9) and obese (4.3 ± 1.1) women and overweight (2.8 ± 1.2) and obese (5.0 ± 3.1) men showed insulin resistance according to HOMA-IR. Significant correlation between leptin and HOMA-IR was found (p = 0.41). BMI, BFP, VFA, WC, and WHtR positively correlated with leptin (p = 0.67, 0.75, 0.66, 0.60, 0.67, respectively) and insulin (p = 0.37, 0.40, 0.48, 0.49, 0.42, respectively), while WHR only with insulin (p = 0.43). No significant differences were found in the other adipokines. Conclusion: the use of health indicators such VFA, WC, WHR, WHtR and HOMA-IR are useful tools in the determination of health, cardio vascular and metabolic risk and are correlated with levels of leptin and insulin in the studied population.

INTRODUCCIÓN: Introducción: el objetivo de este estudio fue evaluar la ingesta de nutrientes, parámetros antropométricos, indicadores de salud, adipocinas y niveles de insulina en una población de jóvenes universitarios con una dieta habitual. Método: en este estudio se invitó a participar a 378 jóvenes universitarios. Debido a los criterios de inclusión y su propia decisión de participar, 90 asistieron a los estudios antropométricos y de indicadores de salud: circunferencia de cintura (WC), índice de cadera cintura (WHR), índice de cintura-talla (WHtR) y modelo homeostático de evaluación-índice de resistencia a la insulina (HOMA-IR) y completaron el cuestionario de frecuencia de ingesta de alimentos. Treinta y cuatro participantes fueron seleccionados para realizar la determinación de los parámetros bioquímicos, niveles de insulina y adipocinas (leptina, IL-6, IL-8, factor de necrosis tumoral alfa [TNF-α], proteína quimioatractante de monocitos-1 [MCP-1] y factor de crecimiento hepático [HGF]). Resultados: de acuerdo con WC, WHR y WHtR, la población obesa mostró riesgo cardiovascular, metabólico y para la salud. La población con sobrepeso mostró riesgo cardiometabólico. En general, la ingesta de lípidos fue superior al 30% y la grasa animal fue la más consumida. Los niveles de leptina (mujeres: 17,2 ± 9,2, 28 ± 11,3, 36,8 ± 17,8; hombres: 4,3 ± 3,6, 9,5 ± 3,1, 24,6 ± 16,4 para delgados, sobrepeso y obesos, respectivamente) e insulina (mujeres: 408 ± 182, 438 ± 187, 768 ± 167; hombres: 244 ± 88, 520 ± 256, 853 ± 590) aumentaron junto con el índice de masa corporal (BMI), porcentaje de grasa corporal (BFP), área de grasa visceral (VFA), WC, WHR y WHtR. Las mujeres delgadas (2,4 ± 1,3), con sobrepeso (2,2 ± 0,9) y obesas (4,3 ± 1,1) y los hombres con sobrepeso (2,8 ± 1,2) y obesos (5,0 ± 3,1) mostraron resistencia a la insulina de acuerdo con HOMA-IR. Se encontró una correlación significativa entre leptina y HOMA-IR (p = 0,41). BMI, BFP, VFA, WC y WHtR correlacionaron positivamente con leptina (p = 0,67, 0,75, 0,66, 0,60 y 0,67, respectivamente) e insulina (p = 0,37, 0,40, 0,48, 0,49 y 0,42, respectivamente), mientras que el WHR solo con insulina (p = 0,43). No se encontraron diferencias significativas en las otras adipocinas. Conclusión: el uso de indicadores de salud como VFA, WC, WHR, WHtR y HOMA-IR es una herramienta útil en la determinación del riesgo metabólico, cardiovascular y de salud, y dichos indicadores correlacionaron con los niveles de leptina e insulina en la población estudiada.