Group leader: This e-mail address is being protected from spambots. You need JavaScript enabled to view it (Junior scientist/Fo.ass., PhD)
Members: Jessica Westlund (PhD student), Tobias Gustafsson (PhD student), Megan Livingston (postdoc), Yeu-Jiann Hua (amanuens).

More than 80 percent of the deaths from infectious diseases worldwide are caused by diseases that use mucosal surfaces to enter the body. More vaccines that can protect our mucosal surfaces are hence uyof global priority. Although injectable vaccines can achieve mucosal immunity it is often required that the vaccine is applied directly to mucosa to generate protection against the pathogen. This is case for many gastrointestinal infections. However, to avoid harmful reactions against our commensal gut flora and food proteins, the mucosal immune system has developed suppress immune reactions. These mechanisms need to be overcome, or at least bypassed for mucosal vaccines to generate protection against infections. Interestingly, when exploited in the correct way these mucosal immune dampening mechanisms could be utilized to ameliorate autoimmune diseases through the induction of tolerance.

The white blood cells that generate immunity against recurrent infections are called lymphocytes. To acquire immunity, the lymphocytes have to be instructed correctly. These instructions are given by dendritic cells. These cells are strategically placed directly underneath the layer of cells lining in the intestine. Here the dendritic cells collect information that they then convey to lymphocytes. Once the dendritic cell has gathered enough information they migrate via lymph to a lymph node. Naïve lymphocytes are constantly being transported to lymph nodes through blood. The encounter between these lymphocytes and the dendritic cells loaded with information is crucial for whether immunity or tolerance is induced.  

The aim of my research is to study what factors that influence this encounter between lymphocytes and the intestinal DC. We will use already available mucosal vaccines to study how these affect the activation and migration of mucosal DCs. I will in detail study what takes place in the intestinal mucosa when a vaccine reaches there. Which DCs leave the intestine via lymph following vaccination? Does the vaccine need to directly bind to the DCs? How is the DC affected by the information it gets from other cells that get in contact with the vaccine? What surface structures on the DCs are being used to collect this information? By answering these questions I believe that I can find new ways to improve the efficacy of mucosal vaccines.

Important publications:

Fahlen-Yrlid, L., Gustafsson, T., Hansson, J., Holmberg, A., Strömbeck, A., Blomquist, M., MacPherson, G.G., Holmgren, J. and Yrlid U. (2009). CD11chigh Dendritic Cells Are Essential for Activation of CD4+ T Cells and Generation of Specific Antibodies following Mucosal Immunization. J. Immunol. 183. 5032-5041.

Cucak, H., Yrlid, U., Reizis B., Kalinke U. and Johansson-Lindbom. B (2009). Type I Interferon Signaling in Dendritic Cells Stimulates the Development of Lymph-Node-Resident T Follicular Helper Cells. Immunity 31, 491-501.

Milling S.W.F, Yrlid U., Jenkins C.D., Richards C.M., Williams, N.A. and MacPherson G.G. (2007). Regulation of intestinal immunity: Effects of the oral adjuvant Escherichia coli heat labile enterotoxin on migrating dendritic cells. Eur. J. Immunol. 37, 87-99.

Yrlid U., Cerovic V., Milling S.W.F, Jenkins C.D., Zhang, J., Crocker, P.R., Klavinskis, L.S, and MacPherson G.G. (2006). Plasmacytoid dendritic cells do not migrate in intestinal or hepatic lymph. J. Immunol. 177, 6115-6122.

Yrlid U., Milling S.W.F, Jenkins C.D., Miller J.L., Cartland, S and MacPherson G.G. (2006). Regulation of intestinal dendritic cell migration and activation by plasmacytoid dendritic cells, TNF-alpha and type 1 IFNs after feeding a TLR7/8 ligand. J. Immunol. 176, 5205-5212.

Yrlid U., Jenkins C.D. and MacPherson G.G. (2006). Relationships between distinct blood monocyte subsets and migrating intestinal lymph dendritic cells in vivo under steady state conditions. J. Immunol. 176, 4155-4162.

Yrlid U., Cerovic V., Milling S.W.F, Jenkins C.D., Klavinskis, L.S and MacPherson G.G. (2006). A distinct subset of intestinal dendritic cells responds selectively to oral TLR7/8 stimulation. Eur. J. Immunol. 36, 2639-2648.