The role of innate immunity in allergic and autoimmune diseases 

The focus of our research is the innate immune system.

The questions we are asking are

• i) what molecules and mechanisms contribute to cellular activation by microbial components?

• ii) what role does this activation of the innate immune system play in immunopathology?

• ad i) We are investigating which cell surface molecules contribute to activation of monocytes and macrophages upon recognition of microbial structures, such as lipopolysaccharide (LPS, endotoxin), bacterial lipoprotein, and superantigens (e.g. staphylococcal enterotoxins). Specifically, we are investigating how Toll-like receptors (TLR), CD14, and MHC class II-molecules contribute to cell activation. The experimental system we use are monocytic and epithelial cell lines transfected with the molecules under investigation.

• ad ii) The role of the adaptive immune system and its components (T cells, B cells, antibodies) in immunopathology has extensively been studied. The contribution of the the innate immune response to the pathogenesis of autoimmune and allergic diseases has received comparatively little attention.

We have found that exposure to microbes in the environment not only protects children against the develoment of allergies but also has an impact on the expression of CD14 and TLR2. We currently are following up on this observation aiming at elucidating mechanisms of the innate immune response potentially influencing the development of allergies. Furthermore, we found that synovial cells express increased levels of TLR2 and can be activated through TLR2. We now are investigating mechanisms underlying a possible contribution of the innate immune response to the development of autoimmune diseases.

Publications

Lauener R.P., T. Birchler, J. Adamski, C. Braun-Fahrländer, A. Bufe, U. Herz, E. von Mutius, D. Nowak, J. Riedler, M. Waser, F.H. Sennhauser, and the ALEX study group. 2002. Expression of CD14 and Toll-like receptor 2 differs between farmers' and non-farmers' children. The Lancet 360:465-466

Seibl R, Birchler T, Loeliger S, Hossle JP, Gay RE, Saurenmann T, Michel BA, Seger RA, Gay S, Lauener RP. Expression and regulation of toll-like receptor 2 in rheumatoid arthritis synovium. 2003. .Am J Pathol: 162(4):1221-7

Contacts

Dr. R. Lauener (Project Leader)
roger.lauenerkispi.uzh.ch