Research findings for chronic inflammatory bowel disease
Researchers at the University of Basel, Clarunis – University Center for Gastrointestinal and Liver Diseases, Basel, and the Swedish Karolinska Institute demonstrate how macrophages in the intestinal mucosa contribute towards chronic inflammatory bowel disease by recognising endogenous or microbial metabolic products. The G-Protein coupled receptor GPR35 plays a key role in this. The study was published in the renowned journal "Cell Reports".
Targeted manipulation of GPR35 for possible future therapies
The research group led by Prof. Jan Niess, consultant in gastroenterology/hepatology at Clarunis – University Center for Gastrointestinal and Liver Diseases, Basel, researched the following in collaboration with colleagues at the Karolinska Institute led by Prof. Eduardo Villablanca, Sweden, in a translational study: What impact does the deactivation of GPR35 have on bowel inflammation? How does the activation of GPR35 influence chronic inflammatory bowel disease?
When GPR35 is purposefully deactivated in macrophages, these macrophages, stimulated by metabolic products, surprisingly form fewer tumour necrosis factors, molecular cues which contribute towards an inflammatory reaction. The reduced production of tumour necrosis factors in macrophages is linked to a reduction in the production of corticosteroids in the intestinal mucosa. The inflammatory reaction is therefore not deactivated.
The analysis of data from the Swiss IBD Cohort Study Group showed that chronic inflammatory bowel disease with a hyperactive GPR35 receptor exhibits higher inflammatory activity. The researchers conclude that the deactivation, as well as an uncontrolled activation, of GPR35 promotes the onset of bowel inflammation.
The researchers hope that the targeted manipulation of GPR35 will in future present new opportunities for the treatment of chronic inflammatory bowel disease. Pharmacological characterisation of GPR35 may in future make it possible to inhibit a hyperactive GPR35 or stimulate an inactive GPR35 in order to regulate inflammatory reaction in the bowel. Antibodies or small molecules could be used for this.
Original publication
Berna Kaya, Cristian Doñas Cuadra, Philipp Wuggenig, Oscar E. Diaz, Rodrigo A. Morales, Hassan Melhem, Swiss IBD Cohort Investigators, Pedro P. Hernández, Tanay Kaymak, Srustidhar Das, Petr Hruz, Yannick Franc, Florian Geier, C. Korcan Ayata, Eduardo J. Villablanca, Jan Hendrik Niess. Lysophosphatidic Acid-Mediated GPR35 Signaling in CX3CR1+ Macrophages Regulates Intestinal Homeostasis. Cell Reports 2020 Aug 4;32(5):107979 https://doi.org/10.1016/j.celrep.2020.107979
Further information
Prof. Jan Hendrik Niess, University of Basel and Clarunis, email: janhendrik.niess(at)unibas.ch