IgE-mediated type I hypersensitivity reactions have many reported beneficial functions in the immune defense against parasites, venoms, toxins etc. However, they are best-known for their role in allergy affecting nowadays almost one third of the population worldwide. IgE-mediated allergic diseases result from a maladaptive type 2 immune response that promotes the synthesis of IgE antibodies directed to a special class of antigens called allergens. IgE antibodies bind to type I high affinity IgE receptors (FcepsilonRI) on mast cells and basophils licensing them to get triggered in a subsequent encounter with the cognate allergen. This promotes the release of a whole set of inflammatory mediators including histamine responsible for the symptoms of immediate hypersensitivity. The development of type 2 driven allergies are dependent on a complex interplay of genetic and environmental factors at barrier surfaces including the host microbiome that builds up during early life. While without doubt IgE-mediated immediate hypersensitivity reactions are at the origin of the majority of allergies it has become clear that similar responses and symptoms can be triggered by other types of adaptive immune responses mediated via IgG or complement involving other immune cells and mediators. Likewise, various innate triggers via receptors expressed on mast cells have been found either to directly launch an allergic reaction and/or to amplify existing IgE-mediated responses. This review summarizes recent findings on both IgE-dependent and IgE-independent mechanisms in the development of allergies and provides an update on allergy diagnosis.

A sizable part (~2%) of the human genome encodes for proteases. They are involved in many physiological processes, such as development, reproduction and inflammation, but also play a role in pathology. Mast cells (MC) contain a variety of MC specific proteases, the expression of which may differ between various MC subtypes. Amongst these proteases, chymase represents up to 25% of the total proteins in the MC and is released from cytoplasmic granules upon activation. Once secreted, it cleaves the targets in the local tissue environment, but may also act in lymph nodes infiltrated by MC, or systemically, when reaching the circulation during an inflammatory response. MC have been recognized as important components in the development of kidney disease. Based on this observation, MC chymase has gained interest following the discovery that it contributes to the angiotensin-converting enzyme’s independent generation of angiotensin II, an important inflammatory mediator in the development of kidney disease. Hence, progress regarding its role has been made based on studies using inhibitors but also on mice deficient in MC protease 4 (mMCP-4), the functional murine counterpart of human chymase. In this review, we discuss the role and actions of chymase in kidney disease. While initially believed to contribute to pathogenesis, the accumulated data favor a more subtle view, indicating that chymase may also have beneficial actions.