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.

Effect of process parameters and operational mode on nitrous oxide emissions from a nitritation reactor treating reject wastewater.

Nitrous oxide (N2O) and methane emissions were monitored in a continuous granular airlift nitritation reactor from ammonium-rich wastewater (reject wastewater). N2O emissions were found to be dependent on dissolved oxygen (DO) concentration in the range of 1-4.5 mg O2/L, increasing within this range when reducing the DO values. At higher DO concentrations, N2O emissions remained constant at 2.2% of the N oxidized to nitrite, suggesting two different mechanisms behind N2O production, one dependent and one independent of DO concentration. Changes on ammonium, nitrite, free ammonia and free nitrous acid concentrations did not have an effect on N2O emissions within the concentration range tested. When operating the reactor in a sequencing batch mode under high DO concentration (>5 mg O2/L), N2O emissions increased one order of magnitude reaching values of 19.3 ± 7.5% of the N oxidized. Moreover, CH4 emissions detected were due to the stripping of the soluble CH4 that remained dissolved in the reject wastewater after anaerobic digestion. Finally, an economical and carbon footprint assessment of a theoretical scaled up of the pilot plant was conducted.