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Tracing the Origins of IgE, Mast Cells, and Allergies by Studies of Wild Animals
Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Mikrobiologi.ORCID-id: 0000-0003-1459-3815
Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Mikrobiologi.
Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Mikrobiologi.ORCID-id: 0000-0002-4771-0080
Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Mikrobiologi.
2017 (Engelska)Ingår i: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 8, artikel-id 1749Artikel, forskningsöversikt (Refereegranskat) Published
Abstract [en]

In most industrialized countries, allergies have increased in frequency quite dramatically during the past 50 years. Estimates show that 20-30% of the populations are affected. Allergies have thereby become one of the major medical challenges of the twenty-first century. Despite several theories including the hygiene hypothesis, there are still very few solid clues concerning the causes of this increase. To trace the origins of allergies, we have studied cells and molecules of importance for the development of IgE-mediated allergies, including the repertoire of immunoglobulin genes. These studies have shown that IgE and IgG most likely appeared by a gene duplication of IgY in an early mammal, possibly 220-300 million years ago. Receptors specific for IgE and IgG subsequently appeared in parallel with the increase in Ig isotypes from a subfamily of the recently identified Fc receptor-like molecules. Circulating IgE levels are generally very low in humans and laboratory rodents. However, when dogs and Scandinavian wolfs were analyzed, IgE levels were found to be 100-200 times higher compared to humans, indicating a generally much more active IgE synthesis in free-living animals, most likely connected to intestinal parasite infections. One of the major effector molecules released upon IgEmediated activation by mast cells are serine proteases. These proteases, which belong to the large family of hematopoietic serine proteases, are extremely abundant and can account for up to 35% of the total cellular protein. Recent studies show that several of these enzymes, including the chymases and tryptases, are old. Ancestors for these enzymes were most likely present in an early mammal more than 200 million years ago before the separation of the three extant mammalian lineages; monotremes, marsupials, and placental mammals. The aim is now to continue these studies of mast cell biology and IgE to obtain additional clues to their evolutionary conserved functions. A focus concerns why the humoral immune response involving IgE and mast cells have become so dysregulated in humans as well as several of our domestic companion animals.

Ort, förlag, år, upplaga, sidor
2017. Vol. 8, artikel-id 1749
Nyckelord [en]
IgE, Fc receptor, mast cell, IgE homeostasis, allergy, dermatitis, asthma
Nationell ämneskategori
Immunologi Immunologi inom det medicinska området Mikrobiologi inom det medicinska området Mikrobiologi
Identifikatorer
URN: urn:nbn:se:uu:diva-347713DOI: 10.3389/fimmu.2017.01749ISI: 000418285800001PubMedID: 29312297OAI: oai:DiVA.org:uu-347713DiVA, id: diva2:1195855
Forskningsfinansiär
Vetenskapsrådet, 621-2011-5007Tillgänglig från: 2018-04-06 Skapad: 2018-04-06 Senast uppdaterad: 2018-04-06Bibliografiskt granskad

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