Control of pro-inflammatory TH17 cells in the small intestine

• Applicant: Professor Dr. Samuel Huber
• Subject Area: Immunology
• Term: from 2013 to 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 230472132

CD4+ T helper cells play an essential role in regulating the immune response. Different types of regulatory T cells have immune suppressive or anti-inflammatory properties. The two most studied subsets are Foxp3+ regulatory T cells (Foxp3+ Treg) and T regulatory type 1 cells (Tr1). On the contrary there are different subtypes of effector CD4+ T helper cells (like TH1, TH2, TH17) which are pro-inflammatory. These pro-inflammatory T helper cells are essential for the defense against micro-organismen. However, if uncontrolled they can cause chronic inflammation and autoimmune disease. One subtype of these effector T helper cells, TH17 cells is particularly associated with chronic inflammatory and autoimmune diseases. However TH17 cells are also crucial for the defense against extra cellular bacteria and fungi. Therefore an endogenous mechanisms controlling these pro-inflammatory TH17 cells seems to be crucial. We recently identified such an endogenous mechanism: We could demonstrate that an overwhelming TH17 immune response, which occurs for example during sepsis, induces a selective recruitment of TH17 cells to the small intestine. Interestingly TH17 could be controlled at that side. Part of the pro-inflammatory TH17 cells was washed out into the intestinal lumen, while the remaining TH17 cells were controlled by Tr1 and Foxp3+ Treg cells. Finally these TH17 acquired a regulatory phenotype (rTH17) with in vitro and in vivo immune suppressive properties. Therefore TH17 cells can switch between a pro- and an anti-inflammatory phenotype, which makes them a very attractive target for immune regulatory therapies. The aim of the proposed project is to analyze this endogenous mechanism controlling TH17 cells. These studies can contribute to the development of new therapeutic strategies for autoimmune and chronic inflammatory diseases.

• DFG Programme: Research Grants