The role of innate lymphoid cells (ILCs) in the modulation of Arthritis by intestinal helminthes

• Applicant: Professor Dr. Mario M. Zaiss
• Subject Area: Rheumatology ; Immunology
• Term: from 2016 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 321820360

With the funding from this grant application I would like to link the research areas of autoimmune diseases (arthritis) and host pathogen interactions (helminths), both of which have captivated me through my scientific career. Innate immune mechanisms in arthritis remain under-investigated. Others and we have shown that helminths induce newly described innate immune cell (ILC) types with potent immune modulating capacity with the theoretical potential to attenuate the severity of arthritis. Therefore, the main research aims are: - To identify ILCs in inflammatory arthritis in humans and mice.- To characterize ILCs in bone turnover. - To evaluate the role of ILCs during inflammatory arthritis on bone turnover and the beneficial impact of helminth infections.In the preliminary experiments for this grant application the in vivo data shows that Heligmosomoides polygyrus can attenuate inflammatory arthritis. We could hypothesize that helminth infections might attenuate inflammatory arthritis and systemic bone turnover by inducing ILCs. This hypothesis provides a possible explanation for our data showing that 2 different helminth species with two different life cycles and infection routes, namely Nippostrongylus brasiliensis and Heligmosomoides polygyrus, have both the potential to attenuate the severity of inflammation and bone destruction as both of them induce ILCs. Moreover could we in preliminary experiments show that a so far unpublished ILC2 knockout mouse strain shows more severe signs of arthritis during an arthritis animal model. Also shows this mouse strain changed systemic bone physiology in the naïve, unchallenged setting, as evident by increased numbers of bone resorbing cells, the osteoclasts. Additionally could we in first experiments translate those findings to the human system by identifying higher ILC2 numbers in serum samples from Arthritis patients. Most importantly, this is further supported by the fact that IL-13 secreted by non-T cells, but possibly by ILC populations is detrimental as shown by a very recent publication from one of my collaborators in this grant application. Understanding the distribution and functional properties of ILCs in inflammatory arthritis will help to identify novel pathways for future therapies. Our findings on ILCs could thus shed new light on fundamental mechanisms that maintain peripheral tolerance in health and are implicated in the development of autoimmunity when they are deregulated or defective.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1937: Innate Lymphoid Cells
• Co-Investigator: Professor Dr. Georg Schett