Effects of IL‐10 on endothelium‐dependent T cell activation have not been investigated in detail. We confirm expression of the IL‐10 receptor and effective signaling via STAT‐3 in human umbilical vein endothelial cells (HUVEC). In CD4 T cell cocultures with HUVEC, pretreatment of endothelial cells with IL‐10 resulted in significant dose‐dependent inhibition of CD4 T cell proliferation, which also occurred when IL‐10 was removed after pretreatment before starting cocultures. Th1/Th2 polarization of proliferated T cells, endothelial nitric oxide (NO), or IL‐12 production were unchanged. However, IL‐10 stimulation resulted in up‐regulation of SOCS‐3, a negative regulator of cytokine secretion, and induction of the inhibitory surface molecules immunoglobulin‐like transcript 3 and 4 (ILT3/ILT4) in EC, potentially involving glucocorticoid‐induced leucine zipper (GILZ). Addition of blocking antibodies against ILT3/ILT4 to EC/T cell cocultures resulted in nearly complete reestablishment of T cell proliferation. In contrast, addition of soluble ILT3 or overexpression of ILT3 in cocultures significantly reduced T cell proliferation. No induction of foxp3+ regulatory T cells was seen. In conclusion, the T cell costimulatory potential of human EC is markedly suppressed by IL‐10 due to up‐regulation of ILT3/ILT4, obviously not involving generation of Treg. This identifies a novel action of IL‐10 in EC and a potential therapeutical target for local immunomodulation.
Background: Peanut allergy has a rising prevalence in high-income countries, affecting 0.5-1.4% of children. This study aimed to better understand peanut anaphylaxis in comparison to anaphylaxis to other food triggers in European children and adolescents. Methods: Data was sourced from the European Anaphylaxis Registry via an online questionnaire, after in-depth review of food induced anaphylaxis cases in a tertiary paediatric allergy centre. Results: 3514 cases of food anaphylaxis were reported between July 2007-March 2018, 56% in patients younger than 18 years. Peanut anaphylaxis was recorded in 459 children and adolescents (85% of all peanut anaphylaxis cases). Previous reactions (42% vs 38%; p=0.001), asthma comorbidity (47% vs 35%; p<0.001), relevant co-factors (29% vs 22%; p=0.004) and biphasic reactions (10% vs 4%; p=0.001) were more commonly reported in peanut anaphylaxis. Most cases were labelled as severe anaphylaxis (Ring&Messmer grade III 65% vs 56% and grade IV 1.1% vs 0.9%; p=0.001). Self-administration of intramuscular adrenaline was low (17% vs 15%), professional adrenaline administration was higher in non-peanut food anaphylaxis (34% vs 26%; p=0.003). Hospitalisation was higher for peanut anaphylaxis (67% vs 54%; p=0.004). Conclusions: The European Anaphylaxis Registry data confirmed peanut as one of the major causes of severe, potentially life-threatening allergic reactions in European children, with some characteristic features e.g. presence of asthma comorbidity and increased rate of biphasic reactions. Usage of intramuscular adrenaline as first line treatment is low and needs to be improved. The Registry, designed as the largest database on anaphylaxis, allows continuous assessment of this condition.
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