BackgroundSuccinate, in addition to its role as an intermediary of the citric acid cycle, acts as an alarmin, initiating and propagating danger signals resulting from tissue injury or inflammatory stimuli. The contribution of this immune sensing pathway to the development of allergic and inflammatory responses is unknown.MethodsEar thickness of wild‐type (wt) and Sucnr1‐deficient (Sucnr1
−/−) mice, sensitized and challenged with oxazolone, was used as a criterion to assess the relevance of SUCNR1/GPR91 expression mediating allergic contact dermatitis (ACD). Results obtained in this system were contrasted with data generated using passive cutaneous anaphylaxis, ovalbumin‐induced asthma and arthritis models.ResultsWe found augmented ACD reactions in Sucnr1
−/− mice. This observation correlated with increased mast cell activation in vitro and in vivo. However, exacerbated mast cell activation in Sucnr1
−/− mice did not contribute to the enhancement of asthma or arthritis and seemed to be due to alterations during mast cell development as augmented mast cell responses could be recapitulated in wt mast cells differentiated in the absence of succinate.ConclusionsA deficiency in succinate sensing during mast cell development confers these cells with a hyperactive phenotype. Such a phenomenon does not translate into exacerbation of asthma or mast cell‐dependent arthritis. On the contrary, the fact that Sucnr1
−/− mice developed reduced arthritic disease, using two different in vivo models, indicates that GPR91 antagonists may have therapeutic potential for the treatment of allergic and autoimmune diseases.
• Tungsten-induced rhEPO aggregates in clinical lots are associated with rhEPOneutralizing antibodies and PRCA.• T-cell responses differentiate nonaggregated from aggregated rhEPO, confirming immunogenicity of tungsten-induced rhEPO aggregates.
The porcine immune system has been studied especially with regard to infectious diseases of the domestic pig, highlighting the economic importance of the pig in agriculture. Recently, in particular, minipigs have received attention as alternative species to dogs or nonhuman primates in drug safety evaluations. The increasing number of new drug targets investigated to modulate immunological pathways has triggered renewed interest to further explore the porcine immune system. Comparative immunological studies of minipigs with other species broaden the translational models investigated in drug safety evaluations. The porcine immune system overall seems functionally similar to other mammalian species, but there are some anatomical, immunophenotypical, and functional differences. Here, we briefly review current knowledge of the innate and adaptive immune system in pigs and minipigs. In conclusion, more systematic and cross-species comparisons are needed to assess the significance of immunological findings in minipigs in the context of translational safety sciences.
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