Analysis of the interaction between invariant natural killer T cells, intestinal microbes and microbial metabolites to prevent allergic airway and intestinal inflammation

• Applicants: Professor Dr. Joachim Saloga, since 1/2024; Professor Dr. Detlef Schuppan
• Subject Area: Rheumatology ; Immunology
• Term: from 2017 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 378702508

Chronic inflammation of the lung and intestine, as is observed in airway and food allergy, is due to loss of tolerance to otherwise harmless allergens. Herein, we recently identified amylase trypsin inhibitors (ATI), water soluble non-gluten proteins in wheat and related cereals, as common nutritional activators of myeloid innate immune cells and as inducers of intestinal dysbiosis. In the first project period we demonstrated that ATI served as adjuvants for allergen-specific immune responses in vitro, and promoted allergic airway as well as intestinal inflammation in a humanized mouse model of allergy in vivo. In this humanized mouse model, we could also show that CD56-expressing invariant natural killer T (iNKT) and likely downstream activated innate lymphoid type 2 (ILC2) cells are critically involved in the development of allergen-induced gut and lung inflammation. Changes in the microbiota by treatment of humanized mice with either the probiotic bacterial formulation BactoFlor® 10/20 or with short-chain fatty acids prevented allergic inflammation. Interestingly, an increased number of iNKT cells was found in the intestine and lungs of germ-free mice, indicating that microbial signals are important to regulate their development. Therefore, in the extension of this project, we want to investigate the interaction of beneficial bacteria represented by BactoFlor® 10/20 and selective immunomodulatory metabolites, which might play an important role in the prevention of allergic diseases, with engrafted human innate cell populations, particularly iNKT cells.

• DFG Programme: Research Grants
• Ehemalige Antragstellerin: Privatdozentin Dr. Iris Bellinghausen, until 12/2023