Allergies and allergen-specific immunotherapy are a research focus at the Paul-Ehrlich-Institut (PEI). Researchers of the PEI have now taken a closer look at food-induced enteritis (allergic enteritis), on which little research has been performed up to now, and published some up-to-date results.
Not only hay fever and allergic asthma but also food allergies are on the increase. Thus, data from the USA point to a 50 percent increase between 1997 and 2011. Food allergies can cause local or systemic reactions (reaction affecting the entire organism). They can affect the skin, the airways, the eyes or the gastrointestinal tract (inducing gastrointestinal symptoms). Gastrointestinal types of food allergies that include allergic enteritis (AE) and colitis are observed most frequently in children with cow’s milk or soy allergies and partly also in adults with allergies to other foods such as hen's eggs or wheat.
While pathological changes are well investigated for food allergy-associated atopic dermatitis and allergic asthma, the pathomechanisms leading to allergic enteritis are hardly understood so far. In addition, treatment options for food allergies are still available only to a limited extent. The only established strategies available up to now include avoiding the allergen or an emergency kit, which the patient is required to take with him permanently. For some food allergies, a specific immune therapy in which constantly increasing doses of the allergen are administered is also in the testing stage.
Suitable animal models are required to gain a better understanding of the immunological processes involved in the development of allergic enteritis. Researchers working in the team of Professor Stefan Vieths, vice president of the PEI, have established a mouse model with hen's egg protein induced allergic enteritis. A certain group of white blood cells – eosinophil granulocytes – can be found in the inflammatory tissues of affected individuals and are used as therapeutic target structures. The researchers from the PEI investigated which chemokine receptors and ligands are involved in controlling these eosinophil granulocytes to the site of the inflammatory changes.
Chemokines are a group of signal proteins which cause cells to migrate. By means of gene analyses, the researchers found out that gene expression, and thus the activity of the chemokine receptor 8 (CCR8) and its binding protein CCL1 (chemokine ligand 1) are upregulated in the inflammatory intestinal tissue, and that CCR8 and its ligand are involved in the enrichment of eosinophil granulocytes in the inflammatory tissues that contribute to the allergy in EA. Results of further investigations with so-called CCR8 knock-out mice, in which the gene for CCR8 was switched off, also show that CCR8 is involved in the development of clinical symptoms in allergic enteritis. However, the results have also revealed that knock-out off CCR8 does not provide a sufficient strategy for the suppression of allergic enteritis, since it upregulates other inflammatory cells.
Up to now, it has not been known that in AE, CCR8 is involved in the migration of eosinophil granulocytes to the site of the inflammatory processes. These finding and other results of the research team may thus make an important contribution to the development of therapies for the treatment of allergic enteritis.
Blanco-Pérez F, Kato Y, Gonzalez-Menendez I, Laiño J, Ohbayashi M, Burggraf M, Krause M, Kirberg J, Iwakura Y, Martella M, Quintanilla-Martinez L, Shibata N, Vieths S, Scheurer S, Toda M (2019): CCR8 leads to eosinophil migration and regulates neutrophil migration in murine allergic enteritis.
Sci Rep 9: 9608.